Storage, recall, and novelty detection of sequences by the hippocampus: Elaborating on the SOCRATIC model to account for normal and aberrant effects of dopamine

Abstract

ABSTRACT:In order to understand how the molecular or cellular defects that underlie a disease of the nervous system lead to the observable symptoms, it is necessary to develop a large-scale neural model. Such a model must specify how specific molecular processes contribute to neuronal function, how neurons contribute to network function, and how networks interact to produce behavior. This is a challenging undertaking, but some limited progress has been made in understanding the memory functions of the hippocampus with this degree of detail. There is increasing evidence that the hippocampus has a special role in the learning of sequences and the linkage of specific memories to context. In the first part of this paper, we review a model (the SOCRATIC model) that describes how the dentate and CA3 hippocampal regions could store and recall memory sequences in context. A major line of evidence for sequence recall is the "phase precession" of hippocampal place cells. In the second part of the paper, we review the evidence for theta-gamma phase coding. According to a framework that incorporates this form of coding, the phase precession is interpreted as cued recall of a discrete sequence of items from long-term memory. The third part of the paper deals with the issue of how the hippocampus could learn memory sequences. We show that if multiple items can be active within a theta cycle through the action of a short-term "buffer," NMDA-dependent plasticity can lead to the learning of sequences presented at realistic item separation intervals. The evidence for such a buffer function is reviewed. An important underlying issue is whether the hippocampal circuitry is configured differently for learning and recall. We argue that there are indeed separate states for learning and recall, but that both involve theta oscillations, albeit in possibly different forms. This raises the question of how neuromodulatory input might switch the hippocampus between learning and recall states and more generally how different neuromodulatory inputs reconfigure the hippocampus for different functions. In the fifth part of this paper we review our studies of dopamine and dopamine/NMDA interactions in the control of synaptic function. Our results show that dopamine dramatically reduces the direct cortical input to CA1 (the perforant path input), while having little effect on the input from CA3. In order to interpret the functional consequences of this pathway-specific modulation, it is necessary to understand the function of CA1 and the role of dopaminergic input from the ventral tegmental area (VTA). In the sixth part of this paper we consider several possibilities and address the issue of how dopamine hyperfunction or NMDA hypofunction, abnormalities that may underlie schizophrenia, might lead to the symptoms of the disease. Relevant to this issue is the demonstrated role of the hippocampus in novelty detection, a function that is likely to depend on sequence recall by the hippocampus. Novelty signals are generated when reality does not match ...

Neurocognitive aging: prior memories hinder new hippocampal encoding

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Hippocampal and neocortical interactions during context discrimination: Electrophysiological evidence from the rat

“…1; O' Keefe and Nadel, 1978;Nadel and Wilner, 1980;Nadel and Payne, 2002) may contribute to a match-mismatch type of analysis that evaluates the present context according to how similar it is to the context that an animal is expecting based on past experience (e.g. Gray, 1982;Vinogradova, 1995;Mizumori et al, 1999bMizumori et al, , 2000Gray, 2000;Lisman and Otmakhova, 2001;Anderson and Jeffery, 2003;Hasselmo et al, 2002;Jeffery et al, 2004;Hasselmo, 2005;Manns et al, 2007). Detected mismatches can be used to identify novel situations and to distinguish different contexts, functions that are necessary to define significant events or episodes.…”

Parallel Loss of Hippocampal LTD and Cognitive Flexibility in a Genetic Model of Hyperdopaminergia

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