Free recall and recognition in a network model of the hippocampus: simulating effects of scopolamine on human memory function

Hasselmo, Michael E.; Wyble, Bradley P.

doi:10.1016/s0166-4328(97)00048-x

Cited by 310 publications

(289 citation statements)

References 140 publications

(275 reference statements)

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“…We have shown that in this framework, the activity in response to an input pattern from the olfactory bulb spreads from anterior to posterior neurons with successive sniff cycles if activity dependent plasticity is allowed on association fibers (Linster, Hasselmo, & Gervais, 1995). In this model, cholinergic suppression of all intrinsic association fibers during learning, as previously proposed Hasselmo, 1995;Hasselmo & Bower, 1993;Hasselmo & Wyble, 1997), interferes with the spread of activity from anterior to posterior neurons in the model. This interference with spread of activity slows or blocks the formation of self-organized representations in posterior neurons (Fig.…”

Section: Effect Of Selective Cholinergic Suppression Of Previously Pomentioning

confidence: 81%

Enhanced cholinergic suppression of previously strengthened synapses enables the formation of self-organized representations in olfactory cortex

Linster

Maloney

Patil

et al. 2003

Neurobiology of Learning and Memory

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Computational modeling assists in analyzing the specific functional role of the cellular effects of acetylcholine within cortical structures. In particular, acetylcholine may regulate the dynamics of encoding and retrieval of information by regulating the magnitude of synaptic transmission at excitatory recurrent connections. Many abstract models of associative memory function ignore the influence of changes in synaptic strength during the storage process and apply the effect of these changes only during a socalled recall-phase. Efforts to ensure stable activity with more realistic, continuous updating of the synaptic strength during the storage process have shown that the memory capacity of a realistic cortical network can be greatly enhanced if cholinergic modulation blocks transmission at synaptic connections of the association fibers during the learning process. We here present experimental data from an olfactory cortex brain slice preparation showing that previously potentiated fibers show significantly greater suppression (presynaptic inhibition) by the cholinergic agonist carbachol than unpotentiated fibers. We conclude that low suppression of non-potentiated fibers during the learning process ensures the formation of self-organized representations in the neural network while the higher suppression of previously potentiated fibers minimizes interference between overlapping patterns. We show in a computational model of olfactory cortex, that, together, these two phenomena reduce the overlap between patterns that are stored within the same neural network structure. These results further demonstrate the contribution of acetylcholine to mechanisms of cortical plasticity. The results are consistent with the extensive evidence supporting a role for acetylcholine in encoding of new memories and enhancement of response to salient sensory stimuli.

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Section: Effect Of Selective Cholinergic Suppression Of Previously Pomentioning

confidence: 81%

Enhanced cholinergic suppression of previously strengthened synapses enables the formation of self-organized representations in olfactory cortex

Linster

Maloney

Patil

et al. 2003

Neurobiology of Learning and Memory

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“…In humans, AChmediated modulation is also clearly reduced with normal aging: for example, levels of AChprocessing enzymes are decreased in the hippocampus [49]. In young individuals, modulation by ACh is believed to be crucial for switching between modes of recall and storage within the hippocampus [29], and impaired ACh function in aging might reduce the relative influence of new information in the hippocampus [50,51].…”

Section: Reduced Modulation By the Cholinergic Systemmentioning

confidence: 99%

“…In CA3, the auto-associative network of powerful recurrent collaterals promotes completion of the familiar pattern, and reduced cholinergic input releases the CA3 auto-associative fibers from inhibition [29]. Thus, in aged animals, decreased cholinergic input might reduce the relative influence of new information through the perforant path, and subsequently favor the reactivation of stored information in the CA3 auto-associative network [50,51]. Reduced ACh-mediated modulation, in combination with fewer external details arriving at the reduced number of entorhinal synapses, might therefore bias the aged CA3 subregion towards maintenance of the original representation, and this is exemplified by rigidity of CA3 place cells [82].…”

Section: Ca3mentioning

confidence: 99%

Neurocognitive aging: prior memories hinder new hippocampal encoding

Wilson

Gallagher

Eichenbaum

et al. 2006

Trends in Neurosciences

304

327

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Normal aging is often accompanied by impairments in forming new memories, and studies of aging rodents have revealed structural and functional changes to the hippocampus that might point to the mechanisms behind such memory loss. In this article, we synthesize recent neurobiological and neurophysiological findings into a model of the information-processing circuit of the aging hippocampus. The key point of the model is that small concurrent changes during aging strengthen the auto-associative network of the CA3 subregion at the cost of processing new information coming in from the entorhinal cortex. As a result of such reorganization in aged memory-impaired individuals, information that is already stored would become the dominant pattern of the hippocampus to the detriment of the ability to encode new information.

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“…C) A greatly sensitized form of LTP is enabled by cholinergic modulation during theta Lisman, 1995, 1996). D) Network connectivity that makes it possible to encode new information without interference from old information is promoted by cholinergic modulation (Hasselmo and Wyble, 1997). Thus, based on all this information, it seems reasonable to suspect that the special properties of the Theta-L state depend, at least in part, on cholinergic modulation.…”

Section: The Argument For Two Theta States: One For Learning and One mentioning

confidence: 99%

“…In recent years, several theories of hippocampal function of great breadth have been developed (Hasselmo and Schnell, 1994;O'Reilly and McClelland, 1994;Levy, 1996;Rolls, 1996;Tsodyks et al, 1996;Hasselmo and Wyble, 1997). These attempt to specify the types of computations and information storage being performed in each hippocampal subfield, and the relationship of these processes to known network, cellular, and synaptic properties.…”

Section: Introductionmentioning

confidence: 99%

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

2001

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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 ...

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Free recall and recognition in a network model of the hippocampus: simulating effects of scopolamine on human memory function

Cited by 310 publications

References 140 publications

Enhanced cholinergic suppression of previously strengthened synapses enables the formation of self-organized representations in olfactory cortex

Enhanced cholinergic suppression of previously strengthened synapses enables the formation of self-organized representations in olfactory cortex

Neurocognitive aging: prior memories hinder new hippocampal encoding

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

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