145 research outputs found
Stochastically Gating Ion Channels Enable Patterned Spike Firing through Activity-Dependent Modulation of Spike Probability
The transformation of synaptic input into patterns of spike output is a
fundamental operation that is determined by the particular complement of ion
channels that a neuron expresses. Although it is well established that
individual ion channel proteins make stochastic transitions between conducting
and non-conducting states, most models of synaptic integration are
deterministic, and relatively little is known about the functional consequences
of interactions between stochastically gating ion channels. Here, we show that a
model of stellate neurons from layer II of the medial entorhinal cortex
implemented with either stochastic or deterministically gating ion channels can
reproduce the resting membrane properties of stellate neurons, but only the
stochastic version of the model can fully account for perithreshold membrane
potential fluctuations and clustered patterns of spike output that are recorded
from stellate neurons during depolarized states. We demonstrate that the
stochastic model implements an example of a general mechanism for patterning of
neuronal output through activity-dependent changes in the probability of spike
firing. Unlike deterministic mechanisms that generate spike patterns through
slow changes in the state of model parameters, this general stochastic mechanism
does not require retention of information beyond the duration of a single spike
and its associated afterhyperpolarization. Instead, clustered patterns of spikes
emerge in the stochastic model of stellate neurons as a result of a transient
increase in firing probability driven by activation of HCN channels during
recovery from the spike afterhyperpolarization. Using this model, we infer
conditions in which stochastic ion channel gating may influence firing patterns
in vivo and predict consequences of modifications of HCN
channel function for in vivo firing patterns
From Rapid Place Learning to Behavioral Performance: A Key Role for the Intermediate Hippocampus
Rapid place encoding by hippocampal neurons, as reflected by place-related firing, has been intensely studied, whereas the substrates that translate hippocampal place codes into behavior have received little attention. A key point relevant to this translation is that hippocampal organization is characterized by functional-anatomical gradients along the septotemporal axis: Whereas the ability of hippocampal neurons to encode accurate place information declines from the septal to temporal end, hippocampal connectivity to prefrontal and subcortical sites that might relate such place information to behavioral-control processes shows an opposite gradient. We examined in rats the impact of selective lesions to relevant parts of the hippocampus on behavioral tests requiring place learning (watermaze procedures) and on in vivo electrophysiological models of hippocampal encoding (long-term potentiation [LTP], place cells). We found that the intermediate hippocampus is necessary and largely sufficient for behavioral performance based on rapid place learning. In contrast, a residual septal pole of the hippocampus, although displaying intact electrophysiological indices of rapid information encoding (LTP, precise place-related firing, and rapid remapping), failed to sustain watermaze performance based on rapid place learning. These data highlight the important distinction between hippocampal encoding and the behavioral performance based on such encoding, and suggest that the intermediate hippocampus, where substrates of rapid accurate place encoding converge with links to behavioral control, is critical to translate rapid (one-trial) place learning into navigational performance
Parallel Computational Subunits in Dentate Granule Cells Generate Multiple Place Fields
A fundamental question in understanding neuronal computations is how dendritic events influence the output of the neuron. Different forms of integration of neighbouring and distributed synaptic inputs, isolated dendritic spikes and local regulation of synaptic efficacy suggest that individual dendritic branches may function as independent computational subunits. In the present paper, we study how these local computations influence the output of the neuron. Using a simple cascade model, we demonstrate that triggering somatic firing by a relatively small dendritic branch requires the amplification of local events by dendritic spiking and synaptic plasticity. The moderately branching dendritic tree of granule cells seems optimal for this computation since larger dendritic trees favor local plasticity by isolating dendritic compartments, while reliable detection of individual dendritic spikes in the soma requires a low branch number. Finally, we demonstrate that these parallel dendritic computations could contribute to the generation of multiple independent place fields of hippocampal granule cells
Tuning of Synaptic Integration in the Medial Entorhinal Cortex to the Organization of Grid Cell Firing Fields
SummaryNeurons important for cognitive function are often classified by their morphology and integrative properties. However, it is unclear if within a single class of neuron these properties tune synaptic responses to the salient features of the information that each neuron represents. We demonstrate that for stellate neurons in layer II of the medial entorhinal cortex, the waveform of postsynaptic potentials, the time window for detection of coincident inputs, and responsiveness to gamma frequency inputs follow a dorsal-ventral gradient similar to the topographical organization of grid-like spatial firing fields of neurons in this area. We provide evidence that these differences are due to a membrane conductance gradient mediated by HCN and leak potassium channels. These findings suggest key roles for synaptic integration in computations carried out within the medial entorhinal cortex and imply that tuning of neural information processing by membrane ion channels is important for normal cognitive function
Molecularly defined circuitry reveals input-output segregation in deep layers of the medial entorhinal cortex
SummaryDeep layers of the medial entorhinal cortex are considered to relay signals from the hippocampus to other brain structures, but pathways for routing of signals to and from the deep layers are not well established. Delineating these pathways is important for a circuit level understanding of spatial cognition and memory. We find that neurons in layers 5a and 5b have distinct molecular identities, defined by the transcription factors Etv1 and Ctip2, and divergent targets, with extensive intratelencephalic projections originating in layer 5a, but not 5b. This segregation of outputs is mirrored by the organization of glutamatergic input from stellate cells in layer 2 and from the hippocampus, with both preferentially targeting layer 5b over 5a. Our results suggest a molecular and anatomical organization of input-output computations in deep layers of the MEC, reveal precise translaminar microcircuitry, and identify molecularly defined pathways for spatial signals to influence computation in deep layers
Organization of connectivity of the rat presubiculum: I. Efferent projections to the medial entorhinal cortex
Bombesin facilitates GABAergic transmission and depresses epileptiform activity in the entorhinal cortex
Functional neuroanatomy of the parahippocampal region: The lateral and medial entorhinal areas
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