Recent studies that inactivated the interposed nuclei (IN) demonstrated that blocking the interme... more Recent studies that inactivated the interposed nuclei (IN) demonstrated that blocking the intermediate cerebellum also interrupts CR extinction. Is this extinction deficit related to interrupting the information flow to efferent targets of the IN? To address this question, we inactivated axons of IN neurons in the brachium conjunctivum (BC). This treatment blocked the output of the intermediate cerebellum without directly affecting neurons in the deep cerebellar nuclei. Rabbits were trained in a delay classical conditioning paradigm, using a tone as the conditioned stimulus (CS) and a corneal air puff as the unconditioned stimulus (US). Then, the BC was microinjected with a sodium channel blocker, tetrodotoxin, during 4 extinction sessions in which rabbits were presented only with the CS. Tests performed after the 4-day injection period revealed that CRs did not extinguish in BC inactivation sessions but extinguished at a normal rate in the absence of the drug. CRs were then re-acquired. These data show that the normal flow of information along axons of cerebellar nuclear cells is required for CR extinction. D 2005 Elsevier B.V. All rights reserved.
Recent studies that inactivated the interposed nuclei (IN) demonstrated that blocking the interme... more Recent studies that inactivated the interposed nuclei (IN) demonstrated that blocking the intermediate cerebellum also interrupts CR extinction. Is this extinction deficit related to interrupting the information flow to efferent targets of the IN? To address this question, we inactivated axons of IN neurons in the brachium conjunctivum (BC). This treatment blocked the output of the intermediate cerebellum without directly affecting neurons in the deep cerebellar nuclei. Rabbits were trained in a delay classical conditioning paradigm, using a tone as the conditioned stimulus (CS) and a corneal air puff as the unconditioned stimulus (US). Then, the BC was microinjected with a sodium channel blocker, tetrodotoxin, during 4 extinction sessions in which rabbits were presented only with the CS. Tests performed after the 4-day injection period revealed that CRs did not extinguish in BC inactivation sessions but extinguished at a normal rate in the absence of the drug. CRs were then re-acquired. These data show that the normal flow of information along axons of cerebellar nuclear cells is required for CR extinction. D 2005 Elsevier B.V. All rights reserved.
Acquisition of classically conditioned eyeblink responses (CRs) in the rabbit critically depends ... more Acquisition of classically conditioned eyeblink responses (CRs) in the rabbit critically depends on intermediate cerebellum-related neural circuits. A highly efficient method for determining possible sites of plasticity within eyeblink circuits is the reversible inactivation of circuit components during learning. Inactivation of either the HVI region of the cerebellar cortex or the cerebellar interposed nuclei (IN) during learning is known to prevent CR acquisition. In contrast, inactivating cerebellar efferent axons in the brachium conjunctivum (BC) with small injections of tetrodotoxin (TTX) has been reported to have no effect on CR acquisition. This suggested that the intermediate cerebellum is essential for learning CRs and that activity mediated by the BC is not required for this process. Since we previously found that BC inactivation blocks CR extinction we re-examined its role in CR acquisition. To ensure complete and long-lasting inactivation of the BC, we injected before each training session doses of TTX that were larger than those in the previous acquisition study. Contrary to the previous negative findings, we found that this temporary block of axons in the brachium conjunctivum prevented normal acquisition of CRs. Injecting TTX directly in the adjacent lateral lemniscus, which could possibly influence CR acquisition, had no effect on learning. In addition, a functional test of TTX diffusion around the BC indicated that the inactivation did not affect other known parts of eyeblink circuits, such as the cerebellar interposed nuclei, the middle cerebellar peduncle or the contralateral red nucleus. We conclude that this form of associative learning in the rabbit eyeblink system requires extra-cerebellar learning and/or cerebellar learning that depends on the operation of cerebellar feedback loops.
Classical conditioning of the eyeblink reflex is a form of motor learning that is uniquely depend... more Classical conditioning of the eyeblink reflex is a form of motor learning that is uniquely dependent on the cerebellum. The cerebellar learning hypothesis proposes that plasticity subserving eyeblink conditioning occurs in the cerebellum. The major evidence for this hypothesis originated from studies based on the telecommunications network metaphor of eyeblink circuits. These experiments inactivated parts of cerebellum-related networks during the acquisition and expression of classically conditioned eyeblinks in order to determine sites at which the plasticity occurred. However, recent evidence revealed that these manipulations could be explained by a network performance hypothesis which attributes learning deficits to a non-specific tonic dysfunction of eyeblink networks. Since eyeblink conditioning is mediated by a spontaneously active, recurrent neuronal network with strong tonic interactions, differentiating between the cerebellar learning hypothesis and the network performance hypothesis represents a major experimental challenge. A possible solution to this problem is offered by several promising new approaches that minimize the effects of experimental interventions on spontaneous neuronal activity. Results from these studies indicate that plastic changes underlying eyeblink conditioning are distributed across several cerebellar and extracerebellar regions. Specific input interactions that induce these plastic changes as well as their cellular mechanisms remain unresolved.
Classical conditioning of the eyeblink response in the rabbit is a popular model for studying the... more Classical conditioning of the eyeblink response in the rabbit is a popular model for studying the neural substrates of associative learning. Most of the common eyeblink recording techniques require invasive procedures. To perform experiments in intact animals, a non-invasive, high-speed video recording system was developed to measure eyeblink responses of rabbits during classical conditioning experiments. Besides being non-invasive, this method does not require excessive restraint of the animal. The PC-based system combines a Pulnix video camera with National Instruments video capture and timing hardware to control the experiment and acquire images of the peri-ocular region. The software developed for controlling these experiments also detects the eyeblink by measuring the movement of the upper and lower eyelids, the area of the exposed surface of the eye, and head movements in the sagittal plane. The time resolution of this relatively inexpensive system is 8.33 ms, and at a working distance of 0.8 m, it can detect movements as small as 0.11 mm.
Recent studies that inactivated the interposed nuclei (IN) demonstrated that blocking the interme... more Recent studies that inactivated the interposed nuclei (IN) demonstrated that blocking the intermediate cerebellum also interrupts CR extinction. Is this extinction deficit related to interrupting the information flow to efferent targets of the IN? To address this question, we inactivated axons of IN neurons in the brachium conjunctivum (BC). This treatment blocked the output of the intermediate cerebellum without directly affecting neurons in the deep cerebellar nuclei. Rabbits were trained in a delay classical conditioning paradigm, using a tone as the conditioned stimulus (CS) and a corneal air puff as the unconditioned stimulus (US). Then, the BC was microinjected with a sodium channel blocker, tetrodotoxin, during 4 extinction sessions in which rabbits were presented only with the CS. Tests performed after the 4-day injection period revealed that CRs did not extinguish in BC inactivation sessions but extinguished at a normal rate in the absence of the drug. CRs were then re-acquired. These data show that the normal flow of information along axons of cerebellar nuclear cells is required for CR extinction. D 2005 Elsevier B.V. All rights reserved.
Recent studies that inactivated the interposed nuclei (IN) demonstrated that blocking the interme... more Recent studies that inactivated the interposed nuclei (IN) demonstrated that blocking the intermediate cerebellum also interrupts CR extinction. Is this extinction deficit related to interrupting the information flow to efferent targets of the IN? To address this question, we inactivated axons of IN neurons in the brachium conjunctivum (BC). This treatment blocked the output of the intermediate cerebellum without directly affecting neurons in the deep cerebellar nuclei. Rabbits were trained in a delay classical conditioning paradigm, using a tone as the conditioned stimulus (CS) and a corneal air puff as the unconditioned stimulus (US). Then, the BC was microinjected with a sodium channel blocker, tetrodotoxin, during 4 extinction sessions in which rabbits were presented only with the CS. Tests performed after the 4-day injection period revealed that CRs did not extinguish in BC inactivation sessions but extinguished at a normal rate in the absence of the drug. CRs were then re-acquired. These data show that the normal flow of information along axons of cerebellar nuclear cells is required for CR extinction. D 2005 Elsevier B.V. All rights reserved.
Acquisition of classically conditioned eyeblink responses (CRs) in the rabbit critically depends ... more Acquisition of classically conditioned eyeblink responses (CRs) in the rabbit critically depends on intermediate cerebellum-related neural circuits. A highly efficient method for determining possible sites of plasticity within eyeblink circuits is the reversible inactivation of circuit components during learning. Inactivation of either the HVI region of the cerebellar cortex or the cerebellar interposed nuclei (IN) during learning is known to prevent CR acquisition. In contrast, inactivating cerebellar efferent axons in the brachium conjunctivum (BC) with small injections of tetrodotoxin (TTX) has been reported to have no effect on CR acquisition. This suggested that the intermediate cerebellum is essential for learning CRs and that activity mediated by the BC is not required for this process. Since we previously found that BC inactivation blocks CR extinction we re-examined its role in CR acquisition. To ensure complete and long-lasting inactivation of the BC, we injected before each training session doses of TTX that were larger than those in the previous acquisition study. Contrary to the previous negative findings, we found that this temporary block of axons in the brachium conjunctivum prevented normal acquisition of CRs. Injecting TTX directly in the adjacent lateral lemniscus, which could possibly influence CR acquisition, had no effect on learning. In addition, a functional test of TTX diffusion around the BC indicated that the inactivation did not affect other known parts of eyeblink circuits, such as the cerebellar interposed nuclei, the middle cerebellar peduncle or the contralateral red nucleus. We conclude that this form of associative learning in the rabbit eyeblink system requires extra-cerebellar learning and/or cerebellar learning that depends on the operation of cerebellar feedback loops.
Classical conditioning of the eyeblink reflex is a form of motor learning that is uniquely depend... more Classical conditioning of the eyeblink reflex is a form of motor learning that is uniquely dependent on the cerebellum. The cerebellar learning hypothesis proposes that plasticity subserving eyeblink conditioning occurs in the cerebellum. The major evidence for this hypothesis originated from studies based on the telecommunications network metaphor of eyeblink circuits. These experiments inactivated parts of cerebellum-related networks during the acquisition and expression of classically conditioned eyeblinks in order to determine sites at which the plasticity occurred. However, recent evidence revealed that these manipulations could be explained by a network performance hypothesis which attributes learning deficits to a non-specific tonic dysfunction of eyeblink networks. Since eyeblink conditioning is mediated by a spontaneously active, recurrent neuronal network with strong tonic interactions, differentiating between the cerebellar learning hypothesis and the network performance hypothesis represents a major experimental challenge. A possible solution to this problem is offered by several promising new approaches that minimize the effects of experimental interventions on spontaneous neuronal activity. Results from these studies indicate that plastic changes underlying eyeblink conditioning are distributed across several cerebellar and extracerebellar regions. Specific input interactions that induce these plastic changes as well as their cellular mechanisms remain unresolved.
Classical conditioning of the eyeblink response in the rabbit is a popular model for studying the... more Classical conditioning of the eyeblink response in the rabbit is a popular model for studying the neural substrates of associative learning. Most of the common eyeblink recording techniques require invasive procedures. To perform experiments in intact animals, a non-invasive, high-speed video recording system was developed to measure eyeblink responses of rabbits during classical conditioning experiments. Besides being non-invasive, this method does not require excessive restraint of the animal. The PC-based system combines a Pulnix video camera with National Instruments video capture and timing hardware to control the experiment and acquire images of the peri-ocular region. The software developed for controlling these experiments also detects the eyeblink by measuring the movement of the upper and lower eyelids, the area of the exposed surface of the eye, and head movements in the sagittal plane. The time resolution of this relatively inexpensive system is 8.33 ms, and at a working distance of 0.8 m, it can detect movements as small as 0.11 mm.
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Papers by Gary Zenitsky