scholarly journals Theta-frequency selectivity in the somatic spike-triggered average of rat hippocampal pyramidal neurons is dependent on HCN channels

2017 ◽  
Vol 118 (4) ◽  
pp. 2251-2266 ◽  
Author(s):  
Anindita Das ◽  
Rishikesh Narayanan

The ability to distill specific frequencies from complex spatiotemporal patterns of afferent inputs is a pivotal functional requirement for neurons residing in networks receiving frequency-multiplexed inputs. Although the expression of theta-frequency subthreshold resonance is established in hippocampal pyramidal neurons, it is not known if their spike initiation dynamics manifest spectral selectivity, or if their intrinsic properties are tuned to process gamma-frequency inputs. Here, we measured the spike-triggered average (STA) of rat hippocampal pyramidal neurons through electrophysiological recordings and quantified spectral selectivity in their spike initiation dynamics and their coincidence detection window (CDW). Our results revealed strong theta-frequency selectivity in the STA, which was also endowed with gamma-range CDW, with prominent neuron-to-neuron variability that manifested distinct pairwise dissociations and correlations with different intrinsic measurements. Furthermore, we demonstrate that the STA and its measurements substantially adapted to the state of the neuron defined by its membrane potential and to the statistics of its afferent inputs. Finally, we tested the effect of pharmacologically blocking the hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels on the STA and found that the STA characteristic frequency reduced significantly to the delta-frequency band after HCN channel blockade. This delta-frequency selectivity in the STA emerged in the absence of subthreshold resonance, which was abolished by HCN channel blockade, thereby confirming computational predictions on the dissociation between these two forms of spectral selectivity. Our results expand the roles of HCN channels to theta-frequency selectivity in the spike initiation dynamics, apart from underscoring the critical role of interactions among different ion channels in regulating neuronal physiology. NEW & NOTEWORTHY We had previously predicted, using computational analyses, that the spike-triggered average (STA) of hippocampal neurons would exhibit theta-frequency (4–10 Hz) spectral selectivity and would manifest coincidence detection capabilities for inputs in the gamma-frequency band (25–150 Hz). Here, we confirmed these predictions through direct electrophysiological recordings of STA from rat CA1 pyramidal neurons and demonstrate that blocking HCN channels reduces the frequency of STA spectral selectivity to the delta-frequency range (0.5–4 Hz).

2008 ◽  
Vol 8 (6) ◽  
pp. 170-172
Author(s):  
Gregory C. Mathews

Subunit-Specific Trafficking of >GABAA Receptors During Status Epilepticus. Goodkin HP, Joshi S, Mtchedlishvili Z, Brar J, Kapur J. J Neurosci 2008 5;28(10):2527–2538. It is proposed that a reduced surface expression of GABAA receptors (GABARs) contributes to the pathogenesis of status epilepticus (SE), a condition characterized by prolonged seizures. This hypothesis was based on the finding that prolonged epileptiform bursting (repetitive bursts of prolonged depolarizations with superimposed action potentials) in cultures of dissociated hippocampal pyramidal neurons (dissociated cultures) results in the increased intracellular accumulation of GABARs. However, it is not known whether this rapid modification in the surface-expressed GABAR pool results from selective, subunit-dependent or nonselective, subunit-independent internalization of GABARs. In hippocampal slices obtained from animals undergoing prolonged SE (SE-treated slices), we found that the surface expression of the GABAR β2/3 and γ2 subunits was reduced, whereas that of the δ subunit was not. Complementary electrophysiological recordings from dentate granule cells in SE-treated slices demonstrated a reduction in GABAR-mediated synaptic inhibition, but not tonic inhibition. A reduction in the surface expression of the γ2 subunit, but not the δ subunit was also observed in dissociated cultures and organotypic hippocampal slice cultures when incubated in an elevated KCl external medium or an elevated KCl external medium supplemented with NMDA, respectively. Additional studies demonstrated that the reduction in the surface expression of the γ2 subunit was independent of direct ligand binding of the GABAR. These findings demonstrate that the regulation of surface-expressed GABAR pool during SE is subunit-specific and occurs independent of ligand binding. The differential modulation of the surface expression of GABARs during SE has potential implications for the treatment of this neurological emergency.


2018 ◽  
Vol 120 (2) ◽  
pp. 576-600 ◽  
Author(s):  
Divyansh Mittal ◽  
Rishikesh Narayanan

Biological heterogeneities are ubiquitous and play critical roles in the emergence of physiology at multiple scales. Although neurons in layer II (LII) of the medial entorhinal cortex (MEC) express heterogeneities in channel properties, the impact of such heterogeneities on the robustness of their cellular-scale physiology has not been assessed. Here, we performed a 55-parameter stochastic search spanning nine voltage- or calcium-activated channels to assess the impact of channel heterogeneities on the concomitant emergence of 10 in vitro electrophysiological characteristics of LII stellate cells (SCs). We generated 150,000 models and found a heterogeneous subpopulation of 449 valid models to robustly match all electrophysiological signatures. We employed this heterogeneous population to demonstrate the emergence of cellular-scale degeneracy in SCs, whereby disparate parametric combinations expressing weak pairwise correlations resulted in similar models. We then assessed the impact of virtually knocking out each channel from all valid models and demonstrate that the mapping between channels and measurements was many-to-many, a critical requirement for the expression of degeneracy. Finally, we quantitatively predict that the spike-triggered average of SCs should be endowed with theta-frequency spectral selectivity and coincidence detection capabilities in the fast gamma-band. We postulate this fast gamma-band coincidence detection as an instance of cellular-scale-efficient coding, whereby SC response characteristics match the dominant oscillatory signals in LII MEC. The heterogeneous population of valid SC models built here unveils the robust emergence of cellular-scale physiology despite significant channel heterogeneities, and forms an efficacious substrate for evaluating the impact of biological heterogeneities on entorhinal network function. NEW & NOTEWORTHY We assessed the impact of heterogeneities in channel properties on the robustness of cellular-scale physiology of medial entorhinal cortical stellate neurons. We demonstrate that neuronal models with disparate channel combinations were endowed with similar physiological characteristics, as a consequence of the many-to-many mapping between channel properties and the physiological characteristics that they modulate. We predict that the spike-triggered average of stellate cells should be endowed with theta-frequency spectral selectivity and fast gamma-band coincidence detection capabilities.


2017 ◽  
Author(s):  
Divyansh Mittal ◽  
Rishikesh Narayanan

ABSTRACTBiological heterogeneities are ubiquitous and play critical roles in the emergence of physiology at multiple scales. Although neurons in layer II (LII) of the medial entorhinal cortex (MEC) express heterogeneities in their channel properties, the impact of such heterogeneities on the robustness of cellular-scale physiology has not been assessed. Here, we performed a 55-parameter stochastic search spanning 9 voltage- or calcium-activated channels to assess the impact of channel heterogeneities on the concomitant emergence of 10 electrophysiological characteristics of LII stellate cells (SCs). We generated 50,000 models and found a heterogeneous subpopulation of 155 valid models to robustly match all electrophysiological signatures. We employed this heterogeneous population to demonstrate the emergence of cellular-scale degeneracy in LII SCs, whereby disparate parametric combinations expressing weak pairwise correlations resulted in similar models. We then assessed the impact of virtually knocking out each channel from all valid models and demonstrate that the mapping between channels and measurements was many-to-many, a critical requirement for the expression of degeneracy. Finally, we quantitatively predict that the spike-triggered average of LII SCs should be endowed with theta-frequency spectral selectivity and coincidence detection capabilities in the fast gamma-band. We postulate this fast gamma-band coincidence detection as an instance of cellular-scale efficient coding, whereby SC response characteristics match the dominant oscillatory signals in LII MEC. The heterogeneous population of valid SC models built here unveils the robust emergence of cellular-scale physiology despite significant channel heterogeneities, and forms an efficacious substrate for evaluating the impact of biological heterogeneities on entorhinal network function.KEY POINTSStellate cells (SC) in layer II (LII) of the medial entorhinal cortex express cellular-scale degeneracy in the concomitant manifestation of several of their unique physiological signatures.Several disparate parametric combinations expressing weak pairwise correlations resulted in models with very similar physiological characteristics, including robust theta-frequency membrane potential oscillations spanning several levels of subthreshold depolarization.Electrophysiological measurements of LII SCs exhibited differential and variable dependencies on underlying channels, and the mapping between channels and measurements was many-to-many.Quantitative predictions point to theta-frequency spectral selectivity and fast gamma-range coincidence detection capabilities in class II/III spike-triggered average of LII SCs, with the postulate for this to be an instance of cellular-scale efficient coding.A heterogeneous cell population that accounts for both channel and intrinsic heterogeneities in LII SCs, which could be employed by network models of entorhinal function to probe the impact of several biological heterogeneities on spatial navigation circuits.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jesús David Urbano-Gámez ◽  
Juan José Casañas ◽  
Itziar Benito ◽  
María Luz Montesinos

AbstractDown syndrome (DS) is the most frequent genetic cause of intellectual disability including hippocampal-dependent memory deficits. We have previously reported hippocampal mTOR (mammalian target of rapamycin) hyperactivation, and related plasticity as well as memory deficits in Ts1Cje mice, a DS experimental model. Here we characterize the proteome of hippocampal synaptoneurosomes (SNs) from these mice, and found a predicted alteration of synaptic plasticity pathways, including long term depression (LTD). Accordingly, mGluR-LTD (metabotropic Glutamate Receptor-LTD) is enhanced in the hippocampus of Ts1Cje mice and this is correlated with an increased proportion of a particular category of mushroom spines in hippocampal pyramidal neurons. Remarkably, prenatal treatment of these mice with rapamycin has a positive pharmacological effect on both phenotypes, supporting the therapeutic potential of rapamycin/rapalogs for DS intellectual disability.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrés Canales-Johnson ◽  
Renzo C. Lanfranco ◽  
Juan Pablo Morales ◽  
David Martínez-Pernía ◽  
Joaquín Valdés ◽  
...  

AbstractMental imagery is the process through which we retrieve and recombine information from our memory to elicit the subjective impression of “seeing with the mind’s eye”. In the social domain, we imagine other individuals while recalling our encounters with them or modelling alternative social interactions in future. Many studies using imaging and neurophysiological techniques have shown several similarities in brain activity between visual imagery and visual perception, and have identified frontoparietal, occipital and temporal neural components of visual imagery. However, the neural connectivity between these regions during visual imagery of socially relevant stimuli has not been studied. Here we used electroencephalography to investigate neural connectivity and its dynamics between frontal, parietal, occipital and temporal electrodes during visual imagery of faces. We found that voluntary visual imagery of faces is associated with long-range phase synchronisation in the gamma frequency range between frontoparietal electrode pairs and between occipitoparietal electrode pairs. In contrast, no effect of imagery was observed in the connectivity between occipitotemporal electrode pairs. Gamma range synchronisation between occipitoparietal electrode pairs predicted subjective ratings of the contour definition of imagined faces. Furthermore, we found that visual imagery of faces is associated with an increase of short-range frontal synchronisation in the theta frequency range, which temporally preceded the long-range increase in the gamma synchronisation. We speculate that the local frontal synchrony in the theta frequency range might be associated with an effortful top-down mnemonic reactivation of faces. In contrast, the long-range connectivity in the gamma frequency range along the fronto-parieto-occipital axis might be related to the endogenous binding and subjective clarity of facial visual features.


1985 ◽  
Vol 1 ◽  
pp. S148
Author(s):  
Yoshihiro Matsuda ◽  
Shigeru Yoshida ◽  
Koichi Fujimura ◽  
Minoru Nakamura

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