Numerous studies have shown that certain types of striatal interneurons play a crucial role in se... more Numerous studies have shown that certain types of striatal interneurons play a crucial role in selection and regulation of striatal output. Striatal Fast-Spiking Interneurons (FSIs) are parvalbumin positive, GABAergic interneurons that constitute less than 1% of the total striatal population. It is becoming increasingly evident that these sparsely distributed neurons exert a strong inhibitory effect on Medium Spiny projection Neurons (MSNs). MSNs in lateral striatum receive direct synaptic input from regions of cortex representing discrete body parts, and show phasic increases in activity during touch or movement of specific body parts. In the present study, we sought to determine whether lateral striatal FSIs identified by their electrophysiological properties, i.e., short-duration spike and fast firing rate (FR), display body part sensitivity similar to that exhibited by MSNs. During video recorded somatosensorimotor exams, each individual body part was stimulated and responses of single neurons were observed and quantified. Individual FSIs displayed patterns of activity related selectively to stimulation of a discrete body part. Most patterns of activity were similar to those exhibited by typical MSNs, but some phasic decreases were observed. These results serve as evidence that some striatal FSIs process information related to discrete body parts and participate in sensorimotor processing by striatal networks that contribute to motor output. Statement of Significance: Parvalbumin positive, striatal FSIs are hypothesized to play an important role in behavior by inhibiting MSNs. We asked a fundamental question regarding information processed during behavior by FSIs: whether FSIs, which preferentially occupy the sensorimotor portion of the striatum, process activity of discrete body parts. Our finding that they do, in a selective manner similar to MSNs, begins to reveal the types of phasic signals that FSI feed forward to projection neurons during striatal processing of cortical input regarding a specific sensorimotor event. These findings suggest new avenues for testing feed-forward inhibition theory as applied to striatum in naturalistic conditions, such as whether FSI decreases facilitate excitation of MSNs related to the current movement while FSI increases silence MSNs unrelated to the current movement.
Neural activity recorded in the outer molecular layer of the dentate gyrus changes during the cou... more Neural activity recorded in the outer molecular layer of the dentate gyrus changes during the course of simple and differential auditory discrimination learning. Such neural activity in the form of time-locked evoked potentials to the conditioned auditory stimulus has been correlated with 1) the acquisition, extinction and reconditioning of a simple discrimination task, and 2) maintained performance of a complex differential discrimination task. Several tests examining the possible influences of behavioral variables have indicated that the above neural activity is not generated by gross changes in the behavior of the animal during the different phases of conditioning. The sensory evoked neural activity in the dentate gyrus has been shown to reflect the inputs of two major hippocampal afferents, the septo-hippocampal fibers, and the perforant path. Recent experiments suggest that such activity may represent not only processes which are directly related to the conditioned status of the auditory stimulus in terms of its behavioral significance, but also the pattern of events which has just preceded that stimulus.
Cocaine's effects on striatal neurons related to vertical head movement were studied during a tas... more Cocaine's effects on striatal neurons related to vertical head movement were studied during a task requiring vertical head movement. The proportion of long-distance head movements was increased by low doses but decreased by the high dose, which produced stereotypic head bobbing. At all doses, normally low firing rates related to movement were elevated to a greater degree than were normally high firing rates. At the high dose, normally high firing rates were strongly suppressed, a restriction which may contribute to the decreased behavioral diversity characteristic of stereotypy. q 1997 Elsevier Science B.V.
Individual neurons were recorded extracellularly in the nucleus accumbens NAcc of rats during coc... more Individual neurons were recorded extracellularly in the nucleus accumbens NAcc of rats during cocaine self-administration sessions. NAcc neurons exhibited a variety of phasic changes in firing rate within the few seconds before andror after cocaine self-infusion. Analysis of the topographical distribution of the phasic firing patterns showed that there were no differences between NAcc subterritories in the nature of phasic changes in firing exhibited by neurons in relation to cocaine self-infusion. However, the prevalence of phasic firing was lower in the border regions of the caudal shell and within the caudal shell itself relative to the remainder of the NAcc. q 1997 Elsevier Science B.V.
Single unit recordings in awake, unrestrained rats confirmed and extended previous findings regar... more Single unit recordings in awake, unrestrained rats confirmed and extended previous findings regarding the functional organization of the lateral striatum. In individual electrode tracks, clusters of neurons related functionally to an individual body part were interspersed with clusters related to other body parts. The overlapping distributions of these neurons were arranged somatotopically in the dorsal-ventral dimension. The distribution of hind limb neurons was most dorsal and showed no overlap with the distribution of neurons related to oral sensorimotor activity. Oral representation was most ventral of all body parts and extended to the ventral boundary of the lateral striatum. Representations of other body parts overlapped with that of the hind limb dorsally but differed primarily in the degree to which they extended ventrally. Forelimb representation extended farther ventrally than that of the hind limb, but did not extend as far ventrally as that of the neck. Despite substantial overlap in the dorsal-to-ventral order of hind limb-forelimb-neck-face representations, single neurons showed no evidence of overlap, or convergence, of body parts. These data provide a more complete description of the dorsal-ventral somatotopy in the lateral striatum of the rat, which as shown previously, extends throughout the medial-lateral, and much of the anterior-posterior dimensions of the lateral striatum.
The activity of individual accumbens neurons in rats was recorded in relation to intravenous coca... more The activity of individual accumbens neurons in rats was recorded in relation to intravenous cocaine infusions that were either Ž. response i.e., lever press contingent or response non-contingent. Neural firing was additionally recorded in relation to non-reinforced lever presses. Comparisons of firing under the three conditions showed that operant behavior was necessary and sufficient for preinfusion firing to occur. Surprisingly, the same was true, in many cases, for firing that occurred during the infusion. For other neurons, firing during the infusion was unrelated to operant behavior and possibly related to infusion stimuli. The relationship to operant behavior exhibited by the majority of NAcc neurons is consistent with previous studies that demonstrated a necessary relationship between NAcc neurons and cocaine reinforced operant behavior.
Lateral striatal neurons that fire phasically in relation to active movement of the contralateral... more Lateral striatal neurons that fire phasically in relation to active movement of the contralateral forelimb (determined via daily sensorimotor examination) were studied during acquisition of cued lever pressing. Rats were trained to lift the contralateral forepaw from the floor to press a lever in the presence of a tone. The tone was presented 70 times per day (session) for 18 consecutive days. All animals acquired the task, evidenced by gradual improvements across sessions and eventual asymptotic levels in tone discrimination, reaction time, and efficiency of the lever press. Forelimb neurons fired in relation to the lever press during early sessions of acquisition but not after repeated sessions on the task. This difference in firing could not be attributed to differences in forelimb movements during lever pressing or to sampling from different populations of neurons in early versus late sessions. In view of evidence that striatal damage impairs acquisition of motor skills, the change in firing suggests that the striatal activity present in early sessions may be necessary for the acquisition of, but not the automatic performance of, learned motor responses.
Experiments were conducted which extended previous findings regarding the activity of the perfora... more Experiments were conducted which extended previous findings regarding the activity of the perforant path and its synaptic relationship to the granule cells of the dentate gyrus during conditioning. A differential conditioning paradigm was utilized in which rats were trained to respond to one of two different tone frequencies. Results demonstrated that (1) tone elicited averaged evoked potentials recorded from the perforant path terminal zone in the outer molecular layer of the dentate gyrus were similar for both the positive and negative tones regardless of frequency or reversal of the reinforcement condition; (2) extracellular unit discharge patterns of dentate granule cells were differentially associated with the positive and negative tones as demonstrated by post stimulus histograms (PSHs); (3) this differential pattern of unit discharges could be reversed following establishment of criterion differential behavioral responding after reversal of the reinforcement contingency between the two tone stimuli and (4) the differential unit discharge pattern was not present when behavioral responding was not differentiated to the two tone stimuli, e.g., immediately following reversal of the reinforcement contingency. The results are discussed within the context of other anatomically defined functional circuits within the hippocampus which could serve as the basis for alteration of the non differentiated excitatory perforant path input into a differential dentate granule cell discharge pattern for behaviorally relevant sensory stimuli.
Single cell recordings in awake monkeys and cats have demonstrated that individual body parts are... more Single cell recordings in awake monkeys and cats have demonstrated that individual body parts are represented within striatal subregions receiving projections from somatic sensorimo tor cortex. Literature indicating that the lateral striatum of the rat receives similar cortical inputs and subserves sensorimotor functions prompted a study of whether this subregion
In the cocaine self-administering rat, individual nucleus accumbens (NAcc) neurons exhibit phasic... more In the cocaine self-administering rat, individual nucleus accumbens (NAcc) neurons exhibit phasic changes in firing rate within minutes and/or seconds of lever presses (i.e. slow phasic and rapid phasic changes, respectively). To determine whether neurons that demonstrate these changes during self-administration sessions are differentially distributed in the NAcc, rats were implanted with jugular catheters and microwire arrays in different NAcc subregions (Core, Dorsal Shell, Ventromedial Shell, Ventrolateral Shell or Rostral Pole). Neural recording sessions were typically conducted on Day 13-17 of cocaine self-administration (0.77 mg/kg/0.2mL infusion; fixed-ratio 1 schedule of reinforcement; 6 hr daily sessions). Pre-press rapid phasic firing rate changes were greater in lateral accumbal (core, ventrolateral shell) relative to medial accumbal (dorsal shell, rostral pole shell) subregions. Slow phasic pattern analysis revealed that reversal latencies of neurons that exhibited change + reversal patterns differed mediolaterally: medial NAcc neurons exhibited more early reversals and fewer progressive/late reversals than lateral NAcc neurons. Comparisons of firing patterns within individual neurons across time bases indicated that lateral NAcc pre-press rapid phasic increases were correlated with tonic increases. Tonic decreases were correlated with slow phasic patterns in individual medial NAcc neurons, indicative of greater pharmacological sensitivity of neurons in this region. On the other hand, the bias of the lateral NAcc towards increased pre-press rapid phasic activity coupled with a greater prevalence of tonic increase firing may reflect particular sensitivity of these neurons to excitatory afferent signaling and perhaps differential pharmacological influences on firing rates between regions.
The effects of morphine and the synthetic opioid peptide D-Ala2-MePhe4-Met-O-ol-enkephalin (FK 33... more The effects of morphine and the synthetic opioid peptide D-Ala2-MePhe4-Met-O-ol-enkephalin (FK 33-824) on averaged (AEPS) potentials evoked by a tone and extracellular synaptic potentials (EPSs) in the perforant path, recorded from the outer molecular layer (OM) of the dentate gyrus, were examined in rats trained to respond in an auditory discrimination task. Potentials evoked by a tone were systematically altered by both peripheral (intraperitoneal) and central (intracerebroventricular) administration of opioids. The short-latency negative (N1) component of the average evoked potential was increased in amplitude and the longer-latency negative (N2) component was decreased in amplitude by administration of opioids. At the same time, perforant path extracellular synaptic potentials were enhanced after administration of opioids. The changes in the average evoked potential and extracellular synaptic potentials in the perforant path were reversed by subsequent administration of naloxone. The significance of these results is discussed in terms of a possible role of endogenous opioid peptides in modulating the synaptic efficacy of the perforant path during the transmission of sensory information to the hippocampus from the entorhinal cortex.
Numerous studies have shown that certain types of striatal interneurons play a crucial role in se... more Numerous studies have shown that certain types of striatal interneurons play a crucial role in selection and regulation of striatal output. Striatal Fast-Spiking Interneurons (FSIs) are parvalbumin positive, GABAergic interneurons that constitute less than 1% of the total striatal population. It is becoming increasingly evident that these sparsely distributed neurons exert a strong inhibitory effect on Medium Spiny projection Neurons (MSNs). MSNs in lateral striatum receive direct synaptic input from regions of cortex representing discrete body parts, and show phasic increases in activity during touch or movement of specific body parts. In the present study, we sought to determine whether lateral striatal FSIs identified by their electrophysiological properties, i.e., short-duration spike and fast firing rate (FR), display body part sensitivity similar to that exhibited by MSNs. During video recorded somatosensorimotor exams, each individual body part was stimulated and responses of single neurons were observed and quantified. Individual FSIs displayed patterns of activity related selectively to stimulation of a discrete body part. Most patterns of activity were similar to those exhibited by typical MSNs, but some phasic decreases were observed. These results serve as evidence that some striatal FSIs process information related to discrete body parts and participate in sensorimotor processing by striatal networks that contribute to motor output.
Studies using i.v. cocaine self-administration in rats have documented rapid-phasic changes in th... more Studies using i.v. cocaine self-administration in rats have documented rapid-phasic changes in the firing rate of nucleus accumbens neurons within seconds of cocainereinforced lever presses, as well as changes that occur over the course of the cocaine self-administration experiment, i.e. tonic changes in firing rate. During the self-administration period of the experiment, individual neurons exhibit either a tonic increase, a tonic decrease, or no tonic change in firing rate, relative to the neuron's firing rate during the pre-drug period. We evaluated whether rapid-phasic changes in firing were differentially associated with tonically reduced or tonically elevated firing of nucleus accumbens core and shell neurons in cocaine self-administering rats. Rapid-phasic firing patterns within seconds of the cocaine-reinforced lever press were exhibited predominantly by core neurons that also exhibited tonic increases in firing. Conversely, core neurons that did not exhibit such rapid-phasic firing patterns were more likely to show tonically reduced firing. Moreover, core neurons were more likely than shell neurons to exhibit: 1) tonic increases in firing and 2) rapid-phasic increases in firing preceding the cocaine-reinforced lever press. These differences between accumbens subterritories may be related to their distinct involvement in operant responding; the present findings are consistent with an emerging literature which implicates shell in contextual stimulus-induced responding, and core in processing the instrumental response via its discrete output to classic basal ganglia structures. The distinct tendency of the core to exhibit increased firing, coupled with its dichotomous firing outputs (i.e. tonic decreases without rapid phasic responses or tonic increases with rapid phasic responses), may reflect particular sensitivity of these neurons to excitatory limbic afferent signaling involved in instrumental responding. Enhanced phasic responsivity in the core may be an integral component of the mechanism inherent in normal reward processing which is subverted by chronic drug exposure.
1. To examine the activity of single units in the lateral striatum of the awake rat with respect ... more 1. To examine the activity of single units in the lateral striatum of the awake rat with respect to sensorimotor function, 788 units were recorded during locomotion and passive testing. The focus of this report is on 138 units (18%) that fired in relation to sensorimotor activity of a single limb. The remaining units were related to other body parts (16%), to general body movement (38%), or were unresponsive (28%). 2. Firing rates of limb-related units were near zero during resting behavior but increased markedly during treadmill locomotion. Each of the 138 units exhibited a rhythmic pattern of discharge in phase with the locomotor step cycle. Passive testing revealed that 86/97 units tested (89%) responded to passive manipulation of a single limb, exhibiting increased firing rates. Of these, 77 (90%) were related to contralateral and 9 (10%) to ipsilateral limbs. Sixty-one units (71%) were related to a forelimb and 25 (29%) to a hindlimb. Of the 86 units responding to passive manipulation. 34/48 units tested (71%) also responded to cutaneous stimulation of the same limb but no other part of the body. 3. To study in greater detail the rhythmic unit discharges in phase with the locomotor step cycle, computer-synchronized videotape recordings were used to generate perimovement time histograms constructed around discrete locomotor movements of each limb (n = 17 units). Activity of each unit was shown to be restricted to a specific portion of a particular limb's step cycle. The majority of units discharged throughout (8 units) or during a portion of (3 units) the swing phase, whereas other units fired during a portion of stance (3 units), footfall (2 units), or foot off (1 unit). 1. The specificity of unit firing was further demonstrated by the finding that rhythmic discharges, related to discrete locomotor limb movements in the forward direction, were completely absent during spontaneous deviations such as backward or disrupted locomotion. 5. Units related to limb movement were located in the far lateral, especially the dorsolateral, subregion of the striatum. This subregion extend rostrocaudally from A-P +1.6 to -1.0 mm relative to bregma. No clear somatotopic organization was observed, but this issue requires further study. 6. These results show that functional representations of individual limbs can be demonstrated in the lateral striatum of the rat, within a subregion containing terminals of projections from somatic sensorimotor cortex.(ABSTRACT TRUNCATED AT 400 WORDS)
Somatosensory responsiveness and baseline firing rates of 102 striatal neurons were studied in fr... more Somatosensory responsiveness and baseline firing rates of 102 striatal neurons were studied in freely moving rats. For individual neurons, mean levels of responsiveness and baseline firing fluctuated unpredictably in direction and magnitude and independently of each other throughout an experiment. Following microinjections of apomorphine into the substantia nigra, which were used as a means of reducing nigral output activity, the magnitude of fluctuations in striatal somatosensory responsiveness significantly increased, while the magnitude of fluctuations in baseline firing was unaltered. The receptive zones of 54 neurons studied in control experiments remained stable, whereas receptive zones changed in 12 of 25 neurons studied after apomorphine microinjection. Normal nigrostriatal dopamine transmission appears to selectively restrict the magnitude of fluctuations in responsiveness of striatal neurons to corticostriatal synaptic input and may exert additional control over afferent projections from cutaneous receptive zones to these neurons.
Averaged evoked slow-wave potentials (AEPs) were recorded from various locations within the denta... more Averaged evoked slow-wave potentials (AEPs) were recorded from various locations within the dentate gyrus and CA1 field of the hippocampus of 16 rats during the performance of an operant tone discrimination task. Consistent time-locked tone averaged evoked potentials (AEPs) were recorded from the perforant path zone in the outer molecular layer of the dentate gyrus. Tone AEPs were never present in this region (1) prior to development of the discrimination, (2) during behavioral extinction, or (3) during the performance of other operant behaviors. Results are discussed in terms of the functions of the perforant path in neural and behavioral plasticity.
Averaged sensory-evoked potentials were recorded from the outer molecular layer of the dentate gy... more Averaged sensory-evoked potentials were recorded from the outer molecular layer of the dentate gyrus in naïve rats and in rats conditioned to respond in the presence of an auditory stimulus. Two components (negative peaks) of the potentials were functionally distinguished in terms of responsiveness to unique or conditioned auditory stimuli. Each component was independently generated by a separate input pathway to the dentate gyrus: The perforant path provided an "insignificance" or "unexpected" feature of the sensory stimulus when appropriate, and the septum controlled the development of a second component as a function of the behavioral significance of the stimulus during the acquisition of auditory discrimination behavior. A reciprocal relationship between the peak amplitudes of both components of the average evoked potentials dependent on the relative behavioral significance of the sensory stimulus was observed in all animals during extinction and reconditioning of the sensory discrimination task. The findings indicate that the entorhinal and septal projections to the dentate granule cells are activated differentially by sensory stimuli as a function of their acquired behavioral significance to the animal.
Numerous studies have shown that certain types of striatal interneurons play a crucial role in se... more Numerous studies have shown that certain types of striatal interneurons play a crucial role in selection and regulation of striatal output. Striatal Fast-Spiking Interneurons (FSIs) are parvalbumin positive, GABAergic interneurons that constitute less than 1% of the total striatal population. It is becoming increasingly evident that these sparsely distributed neurons exert a strong inhibitory effect on Medium Spiny projection Neurons (MSNs). MSNs in lateral striatum receive direct synaptic input from regions of cortex representing discrete body parts, and show phasic increases in activity during touch or movement of specific body parts. In the present study, we sought to determine whether lateral striatal FSIs identified by their electrophysiological properties, i.e., short-duration spike and fast firing rate (FR), display body part sensitivity similar to that exhibited by MSNs. During video recorded somatosensorimotor exams, each individual body part was stimulated and responses of single neurons were observed and quantified. Individual FSIs displayed patterns of activity related selectively to stimulation of a discrete body part. Most patterns of activity were similar to those exhibited by typical MSNs, but some phasic decreases were observed. These results serve as evidence that some striatal FSIs process information related to discrete body parts and participate in sensorimotor processing by striatal networks that contribute to motor output. Statement of Significance: Parvalbumin positive, striatal FSIs are hypothesized to play an important role in behavior by inhibiting MSNs. We asked a fundamental question regarding information processed during behavior by FSIs: whether FSIs, which preferentially occupy the sensorimotor portion of the striatum, process activity of discrete body parts. Our finding that they do, in a selective manner similar to MSNs, begins to reveal the types of phasic signals that FSI feed forward to projection neurons during striatal processing of cortical input regarding a specific sensorimotor event. These findings suggest new avenues for testing feed-forward inhibition theory as applied to striatum in naturalistic conditions, such as whether FSI decreases facilitate excitation of MSNs related to the current movement while FSI increases silence MSNs unrelated to the current movement.
Neural activity recorded in the outer molecular layer of the dentate gyrus changes during the cou... more Neural activity recorded in the outer molecular layer of the dentate gyrus changes during the course of simple and differential auditory discrimination learning. Such neural activity in the form of time-locked evoked potentials to the conditioned auditory stimulus has been correlated with 1) the acquisition, extinction and reconditioning of a simple discrimination task, and 2) maintained performance of a complex differential discrimination task. Several tests examining the possible influences of behavioral variables have indicated that the above neural activity is not generated by gross changes in the behavior of the animal during the different phases of conditioning. The sensory evoked neural activity in the dentate gyrus has been shown to reflect the inputs of two major hippocampal afferents, the septo-hippocampal fibers, and the perforant path. Recent experiments suggest that such activity may represent not only processes which are directly related to the conditioned status of the auditory stimulus in terms of its behavioral significance, but also the pattern of events which has just preceded that stimulus.
Cocaine's effects on striatal neurons related to vertical head movement were studied during a tas... more Cocaine's effects on striatal neurons related to vertical head movement were studied during a task requiring vertical head movement. The proportion of long-distance head movements was increased by low doses but decreased by the high dose, which produced stereotypic head bobbing. At all doses, normally low firing rates related to movement were elevated to a greater degree than were normally high firing rates. At the high dose, normally high firing rates were strongly suppressed, a restriction which may contribute to the decreased behavioral diversity characteristic of stereotypy. q 1997 Elsevier Science B.V.
Individual neurons were recorded extracellularly in the nucleus accumbens NAcc of rats during coc... more Individual neurons were recorded extracellularly in the nucleus accumbens NAcc of rats during cocaine self-administration sessions. NAcc neurons exhibited a variety of phasic changes in firing rate within the few seconds before andror after cocaine self-infusion. Analysis of the topographical distribution of the phasic firing patterns showed that there were no differences between NAcc subterritories in the nature of phasic changes in firing exhibited by neurons in relation to cocaine self-infusion. However, the prevalence of phasic firing was lower in the border regions of the caudal shell and within the caudal shell itself relative to the remainder of the NAcc. q 1997 Elsevier Science B.V.
Single unit recordings in awake, unrestrained rats confirmed and extended previous findings regar... more Single unit recordings in awake, unrestrained rats confirmed and extended previous findings regarding the functional organization of the lateral striatum. In individual electrode tracks, clusters of neurons related functionally to an individual body part were interspersed with clusters related to other body parts. The overlapping distributions of these neurons were arranged somatotopically in the dorsal-ventral dimension. The distribution of hind limb neurons was most dorsal and showed no overlap with the distribution of neurons related to oral sensorimotor activity. Oral representation was most ventral of all body parts and extended to the ventral boundary of the lateral striatum. Representations of other body parts overlapped with that of the hind limb dorsally but differed primarily in the degree to which they extended ventrally. Forelimb representation extended farther ventrally than that of the hind limb, but did not extend as far ventrally as that of the neck. Despite substantial overlap in the dorsal-to-ventral order of hind limb-forelimb-neck-face representations, single neurons showed no evidence of overlap, or convergence, of body parts. These data provide a more complete description of the dorsal-ventral somatotopy in the lateral striatum of the rat, which as shown previously, extends throughout the medial-lateral, and much of the anterior-posterior dimensions of the lateral striatum.
The activity of individual accumbens neurons in rats was recorded in relation to intravenous coca... more The activity of individual accumbens neurons in rats was recorded in relation to intravenous cocaine infusions that were either Ž. response i.e., lever press contingent or response non-contingent. Neural firing was additionally recorded in relation to non-reinforced lever presses. Comparisons of firing under the three conditions showed that operant behavior was necessary and sufficient for preinfusion firing to occur. Surprisingly, the same was true, in many cases, for firing that occurred during the infusion. For other neurons, firing during the infusion was unrelated to operant behavior and possibly related to infusion stimuli. The relationship to operant behavior exhibited by the majority of NAcc neurons is consistent with previous studies that demonstrated a necessary relationship between NAcc neurons and cocaine reinforced operant behavior.
Lateral striatal neurons that fire phasically in relation to active movement of the contralateral... more Lateral striatal neurons that fire phasically in relation to active movement of the contralateral forelimb (determined via daily sensorimotor examination) were studied during acquisition of cued lever pressing. Rats were trained to lift the contralateral forepaw from the floor to press a lever in the presence of a tone. The tone was presented 70 times per day (session) for 18 consecutive days. All animals acquired the task, evidenced by gradual improvements across sessions and eventual asymptotic levels in tone discrimination, reaction time, and efficiency of the lever press. Forelimb neurons fired in relation to the lever press during early sessions of acquisition but not after repeated sessions on the task. This difference in firing could not be attributed to differences in forelimb movements during lever pressing or to sampling from different populations of neurons in early versus late sessions. In view of evidence that striatal damage impairs acquisition of motor skills, the change in firing suggests that the striatal activity present in early sessions may be necessary for the acquisition of, but not the automatic performance of, learned motor responses.
Experiments were conducted which extended previous findings regarding the activity of the perfora... more Experiments were conducted which extended previous findings regarding the activity of the perforant path and its synaptic relationship to the granule cells of the dentate gyrus during conditioning. A differential conditioning paradigm was utilized in which rats were trained to respond to one of two different tone frequencies. Results demonstrated that (1) tone elicited averaged evoked potentials recorded from the perforant path terminal zone in the outer molecular layer of the dentate gyrus were similar for both the positive and negative tones regardless of frequency or reversal of the reinforcement condition; (2) extracellular unit discharge patterns of dentate granule cells were differentially associated with the positive and negative tones as demonstrated by post stimulus histograms (PSHs); (3) this differential pattern of unit discharges could be reversed following establishment of criterion differential behavioral responding after reversal of the reinforcement contingency between the two tone stimuli and (4) the differential unit discharge pattern was not present when behavioral responding was not differentiated to the two tone stimuli, e.g., immediately following reversal of the reinforcement contingency. The results are discussed within the context of other anatomically defined functional circuits within the hippocampus which could serve as the basis for alteration of the non differentiated excitatory perforant path input into a differential dentate granule cell discharge pattern for behaviorally relevant sensory stimuli.
Single cell recordings in awake monkeys and cats have demonstrated that individual body parts are... more Single cell recordings in awake monkeys and cats have demonstrated that individual body parts are represented within striatal subregions receiving projections from somatic sensorimo tor cortex. Literature indicating that the lateral striatum of the rat receives similar cortical inputs and subserves sensorimotor functions prompted a study of whether this subregion
In the cocaine self-administering rat, individual nucleus accumbens (NAcc) neurons exhibit phasic... more In the cocaine self-administering rat, individual nucleus accumbens (NAcc) neurons exhibit phasic changes in firing rate within minutes and/or seconds of lever presses (i.e. slow phasic and rapid phasic changes, respectively). To determine whether neurons that demonstrate these changes during self-administration sessions are differentially distributed in the NAcc, rats were implanted with jugular catheters and microwire arrays in different NAcc subregions (Core, Dorsal Shell, Ventromedial Shell, Ventrolateral Shell or Rostral Pole). Neural recording sessions were typically conducted on Day 13-17 of cocaine self-administration (0.77 mg/kg/0.2mL infusion; fixed-ratio 1 schedule of reinforcement; 6 hr daily sessions). Pre-press rapid phasic firing rate changes were greater in lateral accumbal (core, ventrolateral shell) relative to medial accumbal (dorsal shell, rostral pole shell) subregions. Slow phasic pattern analysis revealed that reversal latencies of neurons that exhibited change + reversal patterns differed mediolaterally: medial NAcc neurons exhibited more early reversals and fewer progressive/late reversals than lateral NAcc neurons. Comparisons of firing patterns within individual neurons across time bases indicated that lateral NAcc pre-press rapid phasic increases were correlated with tonic increases. Tonic decreases were correlated with slow phasic patterns in individual medial NAcc neurons, indicative of greater pharmacological sensitivity of neurons in this region. On the other hand, the bias of the lateral NAcc towards increased pre-press rapid phasic activity coupled with a greater prevalence of tonic increase firing may reflect particular sensitivity of these neurons to excitatory afferent signaling and perhaps differential pharmacological influences on firing rates between regions.
The effects of morphine and the synthetic opioid peptide D-Ala2-MePhe4-Met-O-ol-enkephalin (FK 33... more The effects of morphine and the synthetic opioid peptide D-Ala2-MePhe4-Met-O-ol-enkephalin (FK 33-824) on averaged (AEPS) potentials evoked by a tone and extracellular synaptic potentials (EPSs) in the perforant path, recorded from the outer molecular layer (OM) of the dentate gyrus, were examined in rats trained to respond in an auditory discrimination task. Potentials evoked by a tone were systematically altered by both peripheral (intraperitoneal) and central (intracerebroventricular) administration of opioids. The short-latency negative (N1) component of the average evoked potential was increased in amplitude and the longer-latency negative (N2) component was decreased in amplitude by administration of opioids. At the same time, perforant path extracellular synaptic potentials were enhanced after administration of opioids. The changes in the average evoked potential and extracellular synaptic potentials in the perforant path were reversed by subsequent administration of naloxone. The significance of these results is discussed in terms of a possible role of endogenous opioid peptides in modulating the synaptic efficacy of the perforant path during the transmission of sensory information to the hippocampus from the entorhinal cortex.
Numerous studies have shown that certain types of striatal interneurons play a crucial role in se... more Numerous studies have shown that certain types of striatal interneurons play a crucial role in selection and regulation of striatal output. Striatal Fast-Spiking Interneurons (FSIs) are parvalbumin positive, GABAergic interneurons that constitute less than 1% of the total striatal population. It is becoming increasingly evident that these sparsely distributed neurons exert a strong inhibitory effect on Medium Spiny projection Neurons (MSNs). MSNs in lateral striatum receive direct synaptic input from regions of cortex representing discrete body parts, and show phasic increases in activity during touch or movement of specific body parts. In the present study, we sought to determine whether lateral striatal FSIs identified by their electrophysiological properties, i.e., short-duration spike and fast firing rate (FR), display body part sensitivity similar to that exhibited by MSNs. During video recorded somatosensorimotor exams, each individual body part was stimulated and responses of single neurons were observed and quantified. Individual FSIs displayed patterns of activity related selectively to stimulation of a discrete body part. Most patterns of activity were similar to those exhibited by typical MSNs, but some phasic decreases were observed. These results serve as evidence that some striatal FSIs process information related to discrete body parts and participate in sensorimotor processing by striatal networks that contribute to motor output.
Studies using i.v. cocaine self-administration in rats have documented rapid-phasic changes in th... more Studies using i.v. cocaine self-administration in rats have documented rapid-phasic changes in the firing rate of nucleus accumbens neurons within seconds of cocainereinforced lever presses, as well as changes that occur over the course of the cocaine self-administration experiment, i.e. tonic changes in firing rate. During the self-administration period of the experiment, individual neurons exhibit either a tonic increase, a tonic decrease, or no tonic change in firing rate, relative to the neuron's firing rate during the pre-drug period. We evaluated whether rapid-phasic changes in firing were differentially associated with tonically reduced or tonically elevated firing of nucleus accumbens core and shell neurons in cocaine self-administering rats. Rapid-phasic firing patterns within seconds of the cocaine-reinforced lever press were exhibited predominantly by core neurons that also exhibited tonic increases in firing. Conversely, core neurons that did not exhibit such rapid-phasic firing patterns were more likely to show tonically reduced firing. Moreover, core neurons were more likely than shell neurons to exhibit: 1) tonic increases in firing and 2) rapid-phasic increases in firing preceding the cocaine-reinforced lever press. These differences between accumbens subterritories may be related to their distinct involvement in operant responding; the present findings are consistent with an emerging literature which implicates shell in contextual stimulus-induced responding, and core in processing the instrumental response via its discrete output to classic basal ganglia structures. The distinct tendency of the core to exhibit increased firing, coupled with its dichotomous firing outputs (i.e. tonic decreases without rapid phasic responses or tonic increases with rapid phasic responses), may reflect particular sensitivity of these neurons to excitatory limbic afferent signaling involved in instrumental responding. Enhanced phasic responsivity in the core may be an integral component of the mechanism inherent in normal reward processing which is subverted by chronic drug exposure.
1. To examine the activity of single units in the lateral striatum of the awake rat with respect ... more 1. To examine the activity of single units in the lateral striatum of the awake rat with respect to sensorimotor function, 788 units were recorded during locomotion and passive testing. The focus of this report is on 138 units (18%) that fired in relation to sensorimotor activity of a single limb. The remaining units were related to other body parts (16%), to general body movement (38%), or were unresponsive (28%). 2. Firing rates of limb-related units were near zero during resting behavior but increased markedly during treadmill locomotion. Each of the 138 units exhibited a rhythmic pattern of discharge in phase with the locomotor step cycle. Passive testing revealed that 86/97 units tested (89%) responded to passive manipulation of a single limb, exhibiting increased firing rates. Of these, 77 (90%) were related to contralateral and 9 (10%) to ipsilateral limbs. Sixty-one units (71%) were related to a forelimb and 25 (29%) to a hindlimb. Of the 86 units responding to passive manipulation. 34/48 units tested (71%) also responded to cutaneous stimulation of the same limb but no other part of the body. 3. To study in greater detail the rhythmic unit discharges in phase with the locomotor step cycle, computer-synchronized videotape recordings were used to generate perimovement time histograms constructed around discrete locomotor movements of each limb (n = 17 units). Activity of each unit was shown to be restricted to a specific portion of a particular limb's step cycle. The majority of units discharged throughout (8 units) or during a portion of (3 units) the swing phase, whereas other units fired during a portion of stance (3 units), footfall (2 units), or foot off (1 unit). 1. The specificity of unit firing was further demonstrated by the finding that rhythmic discharges, related to discrete locomotor limb movements in the forward direction, were completely absent during spontaneous deviations such as backward or disrupted locomotion. 5. Units related to limb movement were located in the far lateral, especially the dorsolateral, subregion of the striatum. This subregion extend rostrocaudally from A-P +1.6 to -1.0 mm relative to bregma. No clear somatotopic organization was observed, but this issue requires further study. 6. These results show that functional representations of individual limbs can be demonstrated in the lateral striatum of the rat, within a subregion containing terminals of projections from somatic sensorimotor cortex.(ABSTRACT TRUNCATED AT 400 WORDS)
Somatosensory responsiveness and baseline firing rates of 102 striatal neurons were studied in fr... more Somatosensory responsiveness and baseline firing rates of 102 striatal neurons were studied in freely moving rats. For individual neurons, mean levels of responsiveness and baseline firing fluctuated unpredictably in direction and magnitude and independently of each other throughout an experiment. Following microinjections of apomorphine into the substantia nigra, which were used as a means of reducing nigral output activity, the magnitude of fluctuations in striatal somatosensory responsiveness significantly increased, while the magnitude of fluctuations in baseline firing was unaltered. The receptive zones of 54 neurons studied in control experiments remained stable, whereas receptive zones changed in 12 of 25 neurons studied after apomorphine microinjection. Normal nigrostriatal dopamine transmission appears to selectively restrict the magnitude of fluctuations in responsiveness of striatal neurons to corticostriatal synaptic input and may exert additional control over afferent projections from cutaneous receptive zones to these neurons.
Averaged evoked slow-wave potentials (AEPs) were recorded from various locations within the denta... more Averaged evoked slow-wave potentials (AEPs) were recorded from various locations within the dentate gyrus and CA1 field of the hippocampus of 16 rats during the performance of an operant tone discrimination task. Consistent time-locked tone averaged evoked potentials (AEPs) were recorded from the perforant path zone in the outer molecular layer of the dentate gyrus. Tone AEPs were never present in this region (1) prior to development of the discrimination, (2) during behavioral extinction, or (3) during the performance of other operant behaviors. Results are discussed in terms of the functions of the perforant path in neural and behavioral plasticity.
Averaged sensory-evoked potentials were recorded from the outer molecular layer of the dentate gy... more Averaged sensory-evoked potentials were recorded from the outer molecular layer of the dentate gyrus in naïve rats and in rats conditioned to respond in the presence of an auditory stimulus. Two components (negative peaks) of the potentials were functionally distinguished in terms of responsiveness to unique or conditioned auditory stimuli. Each component was independently generated by a separate input pathway to the dentate gyrus: The perforant path provided an "insignificance" or "unexpected" feature of the sensory stimulus when appropriate, and the septum controlled the development of a second component as a function of the behavioral significance of the stimulus during the acquisition of auditory discrimination behavior. A reciprocal relationship between the peak amplitudes of both components of the average evoked potentials dependent on the relative behavioral significance of the sensory stimulus was observed in all animals during extinction and reconditioning of the sensory discrimination task. The findings indicate that the entorhinal and septal projections to the dentate granule cells are activated differentially by sensory stimuli as a function of their acquired behavioral significance to the animal.
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