Heterogeneities in intrinsic excitability and frequency-dependent response properties of granule cells across the blades of the rat dentate gyrus

Abstract

The dentate gyrus (DG), the input gate to the hippocampus proper, is anatomically segregated into three different sectors, namely, the suprapyramidal blade, the crest region, and the infrapyramidal blade. Although there are well-established differences between these sectors in terms of neuronal morphology, connectivity patterns, and activity levels, differences in electrophysiological properties of granule cells within these sectors have remained unexplored. Here, employing somatic whole cell patch-clamp recordings from the rat DG, we demonstrate that granule cells in these sectors manifest considerable heterogeneities in their intrinsic excitability, temporal summation, action potential characteristics, and frequency-dependent response properties. Across sectors, these neurons showed positive temporal summation of their responses to inputs mimicking excitatory postsynaptic currents and showed little to no sag in their voltage responses to pulse currents. Consistently, the impedance amplitude profile manifested low-pass characteristics and the impedance phase profile lacked positive phase values at all measured frequencies and voltages and for all sectors. Granule cells in all sectors exhibited class I excitability, with broadly linear firing rate profiles, and granule cells in the crest region fired significantly fewer action potentials compared with those in the infrapyramidal blade. Finally, we found weak pairwise correlations across the 18 different measurements obtained individually from each of the three sectors, providing evidence that these measurements are indeed reporting distinct aspects of neuronal physiology. Together, our analyses show that granule cells act as integrators of afferent information and emphasize the need to account for the considerable physiological heterogeneities in assessing their roles in information encoding and processing. NEW & NOTEWORTHY We employed whole cell patch-clamp recordings from granule cells in the three subregions of the rat dentate gyrus to demonstrate considerable heterogeneities in their intrinsic excitability, temporal summation, action potential characteristics, and frequency-dependent response properties. Across sectors, granule cells did not express membrane potential resonance, and their impedance profiles lacked inductive phase leads at all measured frequencies. Our analyses also show that granule cells manifest class I excitability characteristics, categorizing them as integrators of afferent information.

Ion-channel regulation of response decorrelation in a heterogeneous multi-scale model of the dentate gyrus

“…To assess the robustness of networks (in performing channel decorrelation) endowed with different forms of heterogeneities to single ionchannel knockouts, we built DG networks endowed with distinct combinations of four different types of heterogeneities ( Fig. 1D ), following the approaches introduced in ( Mishra and Narayanan, 2019 ): intrinsic heterogeneity , where the GC and BC model neurons had widely variable intrinsic parametric combinations, yet yielded physiological measurements that matched their electrophysiological counterparts ( Mishra and Narayanan, 2020b ; Beck et al, 1992 ; Ferrante et al, 2009 ; Aradi and Holmes, 1999 ; Santhakumar et al, 2005 ). As mentioned in earlier sections, this was incorporated into the network by the use of independent MPMOSS algorithms for generating BC and GC models.…”

“…intrinsic heterogeneity , where the GC and BC model neurons had widely variable intrinsic parametric combinations, yet yielded physiological measurements that matched their electrophysiological counterparts ( Mishra and Narayanan, 2020b ; Beck et al, 1992 ; Ferrante et al, 2009 ; Aradi and Holmes, 1999 ; Santhakumar et al, 2005 ). As mentioned in earlier sections, this was incorporated into the network by the use of independent MPMOSS algorithms for generating BC and GC models.…”

“…Especially with reference to afferent connectivity, accumulating lines of evidence point to adult neurogenesis providing a unique substrate for orthogonal, non-overlapping processing and storage of information from upstream cortex ( Li et al, 2017 ; Lodge and Bischofberger, 2019 ; Aimone et al, 2006 , 2009 ; Luna et al, 2019 ), referred to as afferent heterogeneities. The expression of these amplified heterogeneities, in conjunction with specific characteristics of the local network provide substrates for the prevalent postulates and lines of evidence that the DG network endowed with adult neurogenesis is an ideal system to execute response decorrelation and pattern separation ( Li et al (2017) ; Lodge and Bischofberger (2019) ; Aimone et al (2014) ; Aimone et al (2006) ; Aimone et al (2009) ; Sahay et al (2011) ; Leutgeb et al (2007) ; Kropff et al (2015) ; Mishra and Narayanan (2019) ; Mishra and Narayanan (2020b) ).…”

Ion‐channel degeneracy: Multiple ion channels heterogeneously regulate intrinsic physiology of rat hippocampal granule cells

“…All animals were obtained from the in‐house breeding setup at the central animal facility of the Indian Institute of Science. Surgical and electrophysiological procedures were similar to previously established protocols (Ashhad & Narayanan, 2016 ; Mishra & Narayanan, 2020 ; Narayanan & Johnston, 2007 , 2008 ; Rathour et al, 2016 ) and are detailed below.…”

Membrane Resonance in Pyramidal and GABAergic Neurons of the Mouse Perirhinal Cortex

“…Statistical significance was determined, depending on data, by paired or unpaired two-tailed Student's t-test, One-Way ANOVA test followed by Bonferroni post-hoc, or Kruskal-Wallis test with Dunn's multiple comparisons test. To assess pairwise relationship in the parameters under investigation we analyzed the scatterplot matrices of them and computed the correspondent Pearson's correlation coefficients and significance values, as in Mishra and Narayanan (2020). et al (1987) for I h and from Hodgkin and Huxley (1952) for I NaP .…”