Tuning of Synaptic Integration in the Medial Entorhinal Cortex to the Organization of Grid Cell Firing Fields

Garden, Derek L. F.; Dodson, Paul D.; O’Donnell, Cian; White, Martin; Nolan, Matthew F.

doi:10.1016/j.neuron.2008.10.044

Cited by 162 publications

(312 citation statements)

References 52 publications

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“…The meaning and mechanisms for such changes remain to be determined. The gradient is also reversed as compared with the soma of layer II stellate cells (10,12). Although entorhinal cortex stellate cells and CA1 pyramidal cells are not directly connected to each other, these different rules of organization may influence the way the hippocampus and the entorhinal cortex exchange information.…”

Section: Discussionmentioning

confidence: 99%

Differential Dorso-ventral Distributions of Kv4.2 and HCN Proteins Confer Distinct Integrative Properties to Hippocampal CA1 Pyramidal Cell Distal Dendrites

Marcelin

Lugo

Brewster

et al. 2012

Journal of Biological Chemistry

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Background:Information is differentially processed in the dorsal versus ventral hippocampus. Results: Expression levels of Kv4.2 and HCN1 varied and conferred distinct integrative properties to CA1 pyramidal cell dendrites in dorsal and ventral hippocampus. Conclusion: Molecular and physiological differences provide the basis for the specific properties of dorsal and ventral CA1 pyramidal cells. Significance: Channel expression and function enable specific processing roles.

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Section: Discussionmentioning

confidence: 99%

Differential Dorso-ventral Distributions of Kv4.2 and HCN Proteins Confer Distinct Integrative Properties to Hippocampal CA1 Pyramidal Cell Distal Dendrites

Marcelin

Lugo

Brewster

et al. 2012

Journal of Biological Chemistry

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“…Leak channels are largely responsible for the dorsal-ventral input resistance gradients that are used in the medial entorhinal cortex to maintain gradients of integration properties in grid cell firing fields (28). The regulation of specific g L s (TASK1) has been implicated in maintaining resting potential, input resistance, and the adaptive response to hypoxia or stroke development.…”

Section: Discussionmentioning

confidence: 99%

Imbalance of ionic conductances contributes to diverse symptoms of demyelination

Coggan

Prescott

Bartol

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Fast axonal conduction of action potentials in mammals relies on myelin insulation. Demyelination can cause slowed, blocked, desynchronized, or paradoxically excessive spiking that underlies the symptoms observed in demyelination diseases. The diversity and timing of such symptoms are poorly understood, often intermittent, and uncorrelated with disease progress. We modeled the effects of demyelination (and secondary remodeling) on intrinsic axonal excitability using Hodgkin-Huxley and reduced Morris-Lecar models. Simulations and analysis suggested a simple explanation for the breadth of symptoms and revealed that the ratio of sodium to leak conductance, g Na /g L , acted as a four-way switch controlling excitability patterns that included spike failure, single spike transmission, afterdischarge, and spontaneous spiking. Failure occurred when this ratio fell below a threshold value. Afterdischarge occurred at g Na /g L just below the threshold for spontaneous spiking and required a slow inward current that allowed for two stable attractor states, one corresponding to quiescence and the other to repetitive spiking. A neuron prone to afterdischarge could function normally unless it was switched to its "pathological" attractor state; thus, although the underlying pathology may develop slowly by continuous changes in membrane conductances, a discontinuous change in axonal excitability can occur and lead to paroxysmal symptoms. We conclude that tonic and paroxysmal positive symptoms as well as negative symptoms may be a consequence of varying degrees of imbalance between g Na and g L after demyelination. The KCNK family of g L potassium channels may be an important target for new drugs to treat the symptoms of demyelination. O ligodendrocytes and Schwann cells tightly wrap axons at regular intervals to form the myelin sheath that allows for rapid axonal conduction. Neuropathies involving axonal demyelination are characterized by the unraveling of this insulation and can affect both the central nervous system, as in the case of multiple sclerosis (MS), and the peripheral nervous system, as in Guillain-Barré syndrome.Causes of demyelination include immunologic disease processes, as well as lesions such as traumatic nerve damage, nonpenetrating spinal cord injuries, and chronic nerve compression (1-4). Regardless of the precise etiology, clinical presentation often involves negative (loss-of-function) symptoms, including loss of motor control (i.e., paresis) and sensory deficits such as blindness and numbness, as well as positive (gain-of-function) symptoms, including muscle spasms, tactile allodynia, and chronic pain that is constant or paroxysmal (1, 4-7). Which muscles or sensory modalities are affected depends on where in the nervous system the demyelinating lesions develop, but changes in conduction velocity alone are clearly insufficient to explain the breadth of symptoms observed, especially the positive ones. In particular, MS often produces confounding symptoms that can present intermittently, resolving and retu...

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“…The expression profiles of genes encoding adhesion molecules and ion channels 32,43 may determine intrinsic electrophysiological properties of discrete hippocampal neuronal populations, such as the differences in neuronal excitability 45 and synaptic plasticity [46][47] that have been detected along the long axis. For example, hyperpolarisation-activated cation channels HCN1 and HCN2, which mediate hyperpolarization-activated currents (I h ) currents, exhibit dorsoventral expression differences 48 and are important for a spatial function that is dorsoventrally graded [49][50][51] . In general, neurotransmitter receptor expression varies across the long axis for the majority of transmitter systems (Supplementary Table 1).…”

Section: Gene Expression Along the Long Axismentioning

confidence: 99%

Functional organization of the hippocampal longitudinal axis

Witter²,

et al. 2014

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The precise functional role of the hippocampus remains a topic of much debate. According to a dominant view, the dorsal/posterior hippocampus is implicated in memory and spatial navigation and the ventral/anterior hippocampus mediates anxietyrelated behaviours. However, this 'dichotomy view' may need revision. Gene expression studies demonstrate multiple functional domains along the hippocampal long axis, which often exhibit sharply demarcated borders. By contrast, anatomical studies and electrophysiological recordings in rodents suggest that the long-axis is organized along a gradient. Together, these observations suggest a model in which functional long-axis gradients are superimposed on discrete functional domains. This model provides a potential framework to explain and test the multiple functions ascribed to the hippocampus.The hippocampus is a medial temporal lobe structure critically involved in episodic memory and spatial navigation [1][2][3][4][5][6][7] . Its long, curved form is present across all mammalian orders and runs along a dorsal (septal) to ventral (temporal) axis in rodents, corresponding to a posteriorto-anterior axis in humans (FIG. 1a-b). The same basic intrinsic circuitry is maintained throughout the long axis and across species (FIG. 1c). Despite this conserved intrinsic circuitry, the dorsal and ventral portions have different connectivities with cortical and subcortical areas, and this has long posed a question as to whether the hippocampus is functionally uniform along this axis. Here we review cross-species data that show how the seemingly disparate functions ascribed to the hippocampus can be accommodated by a model in which different functional properties exist along the longitudinal axis.The severe memory impairment suffered by patient H.M. following bilateral hippocampal resection 1 led to intensive study 8 of patients and animal models with hippocampal damage, with an ensuing characterisation of hippocampal function in terms of declarative memory 2 , encompassing both episodic and semantic memory. At the same time, however, evidence emerged for a hippocampal role in spatial memory, based on the discovery of hippocampal 'place cells' 9,10 and the demonstration that hippocampal lesions impair spatial memory 4 . Both the declarative memory hypothesis 11 and the spatial mapping hypothesis 12 of hippocampal function proposed a unitary model in which the entire hippocampus is dedicated

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Tuning of Synaptic Integration in the Medial Entorhinal Cortex to the Organization of Grid Cell Firing Fields

Cited by 162 publications

References 52 publications

Differential Dorso-ventral Distributions of Kv4.2 and HCN Proteins Confer Distinct Integrative Properties to Hippocampal CA1 Pyramidal Cell Distal Dendrites

Differential Dorso-ventral Distributions of Kv4.2 and HCN Proteins Confer Distinct Integrative Properties to Hippocampal CA1 Pyramidal Cell Distal Dendrites

Imbalance of ionic conductances contributes to diverse symptoms of demyelination

Functional organization of the hippocampal longitudinal axis

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