Ethanol Alters Spatial Processing of Hippocampal Place Cells: A Mechanism for Impaired Navigation When Intoxicated

Matthews, Douglas B.; Simson, Peter E.; Best, Phillip J.

doi:10.1111/j.1530-0277.1996.tb01660.x

Cited by 63 publications

(42 citation statements)

References 21 publications

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“…We speculate that the hippocampal map in AD does not do its job because the parameters of place field activity fall outside the core of the learning region L bio and therefore cannot reliably encode spatial information. Similarly, acute ethanol intoxication causes place fields to lose their specificity temporarily suppresses place cell firing rate in a dose-dependent manner [37], and the place fields concomittantly lose their spatial specificity [38]; according to our proposed model, the lowest doses of ethanol do not compromise the rat's navigational ability because they allow the place cells still to operate within the learning region. Our model could thus help shed light not only on the process of learning in novel environments, but also on how such abilities can be lost.…”

Section: Discussionmentioning

confidence: 80%

A Topological Paradigm for Hippocampal Spatial Map Formation Using Persistent Homology

et al. 2012

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An animal's ability to navigate through space rests on its ability to create a mental map of its environment. The hippocampus is the brain region centrally responsible for such maps, and it has been assumed to encode geometric information (distances, angles). Given, however, that hippocampal output consists of patterns of spiking across many neurons, and downstream regions must be able to translate those patterns into accurate information about an animal's spatial environment, we hypothesized that 1) the temporal pattern of neuronal firing, particularly co-firing, is key to decoding spatial information, and 2) since co-firing implies spatial overlap of place fields, a map encoded by co-firing will be based on connectivity and adjacency, i.e., it will be a topological map. Here we test this topological hypothesis with a simple model of hippocampal activity, varying three parameters (firing rate, place field size, and number of neurons) in computer simulations of rat trajectories in three topologically and geometrically distinct test environments. Using a computational algorithm based on recently developed tools from Persistent Homology theory in the field of algebraic topology, we find that the patterns of neuronal co-firing can, in fact, convey topological information about the environment in a biologically realistic length of time. Furthermore, our simulations reveal a “learning region” that highlights the interplay between the parameters in combining to produce hippocampal states that are more or less adept at map formation. For example, within the learning region a lower number of neurons firing can be compensated by adjustments in firing rate or place field size, but beyond a certain point map formation begins to fail. We propose that this learning region provides a coherent theoretical lens through which to view conditions that impair spatial learning by altering place cell firing rates or spatial specificity.

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Section: Discussionmentioning

confidence: 80%

A Topological Paradigm for Hippocampal Spatial Map Formation Using Persistent Homology

et al. 2012

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“…For example, visual context-induced activation of hippocampal "place cells", which are involved in learning spatial orientation and in working memory (Thompson et al conditioning, but not tone conditioning at 1-1.5 g/kg; suppression of both contextual and tone conditioning at 2 g/kg 1983; Thompson and Best 1989), is suppressed by a preceding injection of 2.0 g/kg alcohol (Matthews et al 1996). In agreement with these data, a different alcohol sensitivity of divergent types of context preference conditioning has been suggested in a study where 2.0 g/kg alcohol disrupted preference conditioning to visual but not to olfactory context (Rajachandran et al 1993).…”

Section: Animal Models Suggest Hippocampal Involvement In the Amnestimentioning

confidence: 98%

Role of hippocampus in alcohol-induced memory impairment: implications from behavioral and immediate early gene studies

Ryabinin

1998

Psychopharmacology

117

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Acute alcohol intoxication disrupts memory acquisition in humans and laboratory animals. This review summarizes recent behavioral and immediate early gene expression studies addressing the mechanisms of this phenomenon. Most behavioral investigations agree that the amnestic effect of alcohol is due to its preferential detrimental effect on hippocampus-dependent than on hippocampus-independent forms of learning. However, some hippocampal lesion studies contradict these results. Learning in behavioral paradigms is accompanied by induction of c-fos and other immediate early genes in many brain regions of the animal. In contrast, studies on alcohol-mediated changes in expression of this gene confirm selective hippocampal suppression of basal and experience-induced expression of c-fos after acute and repeated administration of alcohol. This hippocampal suppression is in marked contrast with alcohol-mediated induction of c-fos expression in other brain areas. However, the selective suppression of hippocampal gene expression and memory by alcohol is most likely mediated by a number of interacting neurotransmitter systems. Thus, effects of lower doses of alcohol (0.5 g/kg or lower in rats) seem to be preferentially mediated through GABAergic systems. At intermediate doses (0.75-2 g/kg), several other neurotransmitter systems are affected besides GABA. Higher doses lead to none-specific effects, probably involving even more neurotransmitter systems. Elucidation of these neurotransmitter systems will be highly important for developing rational approaches for correction of alcohol-related cognitive disorders.

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“…Furthermore, acute ethanol administration also alters the specificity of hippocampal pyramidal "place" cells (Matthews et al, 1996). Such alterations in hippocampal function have been difficult to reconcile with research showing that hippocampal GABAA receptors are unresponsive to acute ethanol application.…”

mentioning

confidence: 96%

Differential Regulation of GABA_A Receptor Gene Expression by Ethanol in the Rat Hippocampus Versus Cerebral Cortex

Matthews

Devaud

Fritschy

et al. 1998

Journal of Neurochemistry

Self Cite

103

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Abstract:Previous research has shown that chronic ethanol consumption dramatically alters GABAA receptor a, and a 4 subunit gene expression in the cerebral cortex and GABAA receptor a, and a6 subunit gene expression in the cerebellum. However, it is not yet known if chronic ethanol consumption produces similar alterations in GA-BAA receptor gene expression in other brain regions. One brain region of interest is the hippocampus because it has recently been shown that a subset of GABAA receptors in the hippocampus is responsive to pharmacologically relevant concentrations of ethanol. Therefore, we directly compared the effects of chronic ethanol consumption on GABAA receptor subunit gene expression in the hippocampus and cerebral cortex. Furthermore, we investigated whether the duration of ethanol consumption (14 or 40 days) would influence regulation of GABAA receptor gene expression in these two brain regions. Chronic ethanol consumption produced a significant increase in the level of GABAA receptor a4 subunit peptide in the hippocampus following 40 days but not 14 days. The relative expression of hippocampal GABAA receptor a1, a2, a3, /32/3, or Y2 was not altered by either period of chronic ethanol exposure. In marked contrast, chronic ethanol consumption for 40 days significantly increased the relative expression of cerebral cortical GABAA receptor a4 subunits and significantly decreased the relative expression of cerebral cortical GABAA receptor a, subunits. This finding is consistent with previous results following 14 days of chronic ethanol consumption. Hence, chronic ethanol consumption alters GABAA receptor gene expression in the hippocampus but in a different manner from that in either the cerebral cortex or the cerebellum. Furthermore, these alterations are dependent on the duration of ethanol exposure.

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Ethanol Alters Spatial Processing of Hippocampal Place Cells: A Mechanism for Impaired Navigation When Intoxicated

Cited by 63 publications

References 21 publications

A Topological Paradigm for Hippocampal Spatial Map Formation Using Persistent Homology

A Topological Paradigm for Hippocampal Spatial Map Formation Using Persistent Homology

Role of hippocampus in alcohol-induced memory impairment: implications from behavioral and immediate early gene studies

Differential Regulation of GABA_A Receptor Gene Expression by Ethanol in the Rat Hippocampus Versus Cerebral Cortex

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Ethanol Alters Spatial Processing of Hippocampal Place Cells: A Mechanism for Impaired Navigation When Intoxicated

Cited by 63 publications

References 21 publications

A Topological Paradigm for Hippocampal Spatial Map Formation Using Persistent Homology

A Topological Paradigm for Hippocampal Spatial Map Formation Using Persistent Homology

Role of hippocampus in alcohol-induced memory impairment: implications from behavioral and immediate early gene studies

Differential Regulation of GABAA Receptor Gene Expression by Ethanol in the Rat Hippocampus Versus Cerebral Cortex

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Differential Regulation of GABA_A Receptor Gene Expression by Ethanol in the Rat Hippocampus Versus Cerebral Cortex