Memory systems in the brain and localization of a memory

Neurobiology of Learning and Memory, 2001

Psychological Review, 1992

Hippocampal participation in classical conditioning is described in terms of a multilayer network that portrays stimulus configuration. The network (a) describes behavior in real time, (b) incorporates a layer of "hidden" units positioned between input and output units, (c) includes inputs that are connected to the output directly as well as indirectly through the hidden-unit layer, and (d) uses a biologically plausible backpropagation procedure to train the hidden-unit layer. Nodes and connections in the neural network are mapped onto regional cerebellar, cortical, and hippocampal circuits, and the effect of lesions of different brain regions is formally studied. Computer simulations of the following classical conditioning paradigms are presented: acquisition of delay and trace conditioning, extinction, acquisition-extinction series of delay conditioning, blocking, overshadowing, discrimination acquisition, discrimination reversal, feature-positive discrimination, conditioned inhibition, negative patterning, positive patterning, and generalization. The model correctly describes the effect of hippocampal and cortical lesions in many of these paradigms, as well as neural activity in hippocampus and medial septum during classical conditioning. Some of these results might be extended to the description of anterograde amnesia in human patients.

… of Learning and …, 2001

It is well established that the hippocampal formation is critically involved in the acquisition of trace memories, a paradigm in which the conditioned (CS) and unconditioned stimuli (US) are separated by a temporal gap (Solomon et al., 1986). The structure is reportedly not critical for the acquisition of delay memories, where the CS and the US overlap in time (Berger & Orr, 1983; Schmaltz & Theios, 1972). Based on these results, it is often stated that the hippocampus is involved in "filling the gap" or otherwise associating the two stimuli in time. However, in addition to the presence of a temporal gap, there are other differences between trace and delay conditioning. The most apparent difference is that animals require many more trials to learn the trace task, and thus it is inherently more difficult than the delay task. Here, we tested whether the hippocampus was critically involved in delay conditioning, if it was rendered more difficult such that the rate of acquisition was shifted to be analogous to trace conditioning. Groups of rats received excitotoxic lesions to the hippocampus, sham lesions or were left intact. Using the same interstimulus intervals (ISI), control animals required more trials to acquire the trace than the delay task. As predicted, animals with hippocampal lesions were impaired during trace conditioning but not delay conditioning. However, when the delay task was rendered more difficult by extending the ISI (a long delay task), animals with hippocampal lesions were impaired. In addition, once the lesioned animal learned the association between the CS and the US during delay conditioning, it could learn and perform the trace CR. Thus, the role of the hippocampus in classical conditioning is not limited to learning about discontiguous events in time This work was supported by a National Science Foundation Fellowship to A.V.B., the Busch Memorial Fund and the James McKeen Cattel Fund to L.D.M., and NIMH (59970 and 59740), the National Alliance for Research on Schizophrenia and Depression (NARSAD), and the van Ameringen Foundation to T.J.S.

Annals of the New York Academy of Sciences, 1991

The Journal of Neuroscience : The Official Journal of the Society for Neuroscience

Many studies have confirmed the time-limited involvement of the hippocampus in mnemonic processes and suggested that there is reorganization of the responsible brain circuitry during memory consolidation. To clarify such reorganization, we chose trace classical eyeblink conditioning, in which hippocampal ablation produces temporally graded retrograde amnesia. Here, we extended the temporal characterization of retrograde amnesia to other regions that are involved in acquisition during this task: the medial prefrontal cortex (mPFC) and the cerebellum. At a various time interval after establishing the trace conditioned response (CR), rats received an aspiration of one of the three regions. After recovery, the animals were tested for their CR retention. When ablated 1 d after the learning, both the hippocampal lesion and the cerebellar lesion group of rats exhibited a severe impairment in retention of the CR, whereas the mPFC lesion group showed only a slight decline. With an increase i...

Neurotoxicity Research, 2006

Two major memory systems have been recognized over the years (Squire, in Memory and Brain, 1987): the declarative memory system, which is under the control of the hippocampus and related temporal lobe structures, and the procedural or habit memory system, which is under the control of the striatum and its connections (Mishkin et al., in Neurobiology of Learning by G Lynch et al., 1984; Knowlton et al., Science 273:1399, 1996). Most if not all learning tasks studied in animals, however, involve either the performance or the suppression of movement.

Behavioral Neuroscience, 2002

It has been proposed that contextual fear conditioning depends on 2 processes: (a) construction of a conjunctive representation of the features that make up the context and (b) association of the representation with shock. Support for this view comes from studies indicating that prior exposure to the conditioning context facilitates contextual fear conditioning supported by immediate shock. Thus, conditioning produced by immediate shock is to the memory representation of the preexposed context, which is activated by retrieval cues associated with this context. The authors' experiments support this interpretation and indicate that this process depends on an intact hippocampal formation. These results support the hypothesis that the hippocampal formation supports contextual fear conditioning by storing a conjunctive representation of context.

Brain research, 2014

We argue here that we have succeeded in localizing an essential memory trace for a basic form of associative learning and memory - classical conditioning of discrete responses learned with an aversive stimulus - to the anterior interpositus nucleus of the cerebellum. We first identified the entire essential circuit, using eyelid conditioning as the model system, and used reversible inactivation, during training, of critical structures and activation of pathways to localize definitively the essential memory trace. This discovery and the associated studies have: 1) shown that the essential cerebellar circuit applies equally to all mammals studied, including humans; 2) shown that this cerebellar circuit holds for the learning of any discrete behavioral response elicited by an aversive US, not just eyelid closure; 3) identified the essential circuit and process for reinforcement for this form of learning; 4) shown that this form of learning and its essential cerebellar circuitry is phyl...

Journal of Neuroscience, 2006

Trace conditioning, a form of classical conditioning in which the presentation of the conditioned stimulus (CS) and the unconditioned stimulus (US) is separated in time by an interstimulus interval, requires an intact hippocampus. In contrast, classical conditioning procedures in which the CS and US are not separated by an interstimulus interval (i.e., delay conditioning procedures) typically do not . However, why trace conditioning is dependent on the hippocampus is unknown. Several theories suggest that it is specifically the discontiguity between the CS and US in trace conditioning that critically engages the hippocampus. However, there are other explanations that do not depend on discontiguity. To determine whether the lack of contiguity renders trace conditioning hippocampal dependent, we designed a "contiguous trace conditioning" (CTC) paradigm in which CS-US contiguity is restored by representing the CS simultaneously with the US. Although rats with excitotoxic lesions of the hippocampus could not learn a standard trace fear-conditioning paradigm, lesioned rats trained on CTC showed significant conditioning, at levels similar to those with sham surgeries. Importantly, lesioned rats trained solely with simultaneous CS-US presentations did not demonstrate conditioning. Together, these data suggest that rats with hippocampal lesions can form a memory of a trace CS-US association when contiguity is restored. Therefore, the dependence of traditional trace paradigms on the hippocampus can be attributed to the absence of temporal contiguity.

2019