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

Abstract

Number of words: 249 (Abstract)Abbreviated title: Intrinsic heterogeneities in dentate gyrus granule cells Author contributions P. M. and R. N. designed experiments; P. M. performed experiments; P.M. and R.N. carried out data analysis; P. M. and R. N. co-wrote the paper. ABSTRACTThe 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, 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 less action potentials compared to 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. Aimone JB, Deng W, and Gage FH. Resolving new memories: a critical look at the dentate gyrus, adult neurogenesis, and pattern separation. Neuron 70: 589--596, 2011. Aimone JB, Li Y, Lee SW, Clemenson GD, Deng W, and Gage FH. Regulation and function of adult neurogenesis: from genes to cognition. Physiol Rev 94: 991--1026, 2014. Amaral DG, Scharfman HE, and Lavenex P. The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies). Prog Brain Res 163: 3--22, 2007. Margrie TW. A biophysical signature of network affiliation and sensory processing in mitral cells. Nature 488: 375--378, 2012. Anirudhan A, and Narayanan R. Analogous synaptic plasticity profiles emerge from disparate channel combinations. J Neurosci 35: 4691--4705, 2015. Ashhad S, Johnston D, and Narayanan R. Activation of InsP3 receptors is sufficient for inducing graded intrinsic plasticity in rat hippocampal...

The unique plasticity of hippocampal adult‐born neurons: Contributing to a heterogeneous dentate

“…There are some important anatomical caveats to consider when evaluating much of the work discussed in this review, specifically concerning where within the DG data were collected. For instance, there are differences in connectivity, excitability, inhibition, IEG expression, and levels of neurogenesis between the suprapyramidal versus infrapyramidal blade (Chawla et al, 2005; Claiborne, Amaral, & Cowan, 1986; Mishra & Narayanan, 2020; Ramírez‐Amaya et al, 2005), suggesting the two blades may serve different functional roles (Schmidt, Marrone, & Markus, 2012). An additional major consideration is the location along the dorsal‐ventral axis of the hippocampus.…”

A Sparse, Spatially Biased Subtype of Mature Granule Cell Dominates Recruitment in Hippocampal-Associated Behaviors

“…Such bladespecific recruitment could emerge from underlying cell-intrinsic and/or circuit differences between the blades of the DG, and the activity-predisposed GC subtype we identify here likely uses both mechanisms of preferential recruitment. At the cellintrinsic level, predisposed cells have many differentially expressed genes relative to classical granule cells (Figure S3), which likely underpin differential single-cell computation (Figure 4;Mishra and Narayanan, 2020). At the circuit level, although gross projection differences are not seen between the blades (Scharfman, 2007;van Groen et al, 2003; but see Wyss et al, 1979), the relatively displaced cell bodies and broader dendritic trees likely produce differential integration of long-range inputs.…”

Adult-born neurons promote cognitive flexibility by improving memory precision and indexing

“…Independently from their mode of action, effects of neurogenesis were generally assumed to be homogeneous within the DG. However, recent studies highlighted that adult-born neurons differentially modulate input from the entorhinal cortex into the DG (Luna et al, 2019), which is further supported by an intrinsic heterogeneity in the cellular composition of its infra-vs. supra-pyramidal (IP and SP, respectively) blades (Erwin et al, 2020;Mishra and Narayanan, 2020). Intriguingly, the IP and SP blades are known to preferentially receive input about spatial information or novelty that originate from the medial or lateral entorhinal cortex, respectively (Hargreaves et al, 2005;Knierim et al, 2014;Luna et al, 2019).…”