A synaptic novelty signal to switch hippocampal attractor networks from generalization to discrimination

Abstract

Episodic memory formation and recall are complementary processes that put conflicting requirements on neuronal computations in the hippocampus. How this challenge is resolved in hippocampal circuits is unclear. To address this question, we obtained in vivo whole-cell patch-clamp recordings from dentate gyrus granule cells in head-fixed mice navigating in familiar and novel virtual environments. We find that granule cells consistently show a small transient depolarization of their membrane potential upon transition to a novel environment. This synaptic novelty signal is sensitive to local application of atropine, indicating that it depends on metabotropic acetylcholine receptors. A computational model suggests that the observed transient synaptic response to novel environments may lead to a bias in the granule cell population activity, which can in turn drive the downstream attractor networks to a new state, thereby favoring the switch from generalization to discrimination when faced with novelty. Such a novelty-driven cholinergic switch may enable flexible encoding of new memories while preserving stable retrieval of familiar ones.

A dentate gyrus– CA3 inhibitory circuit promotes evolution of hippocampal-cortical ensembles during memory consolidation

“…(Guo et al, 2018), we propose a testable model for how our manipulation increases synchronous activity of principal neurons in CA1 and ACC. We predict that increasing granule cell recruitment of perisomatic inhibition onto CA3 neurons imposes sparseness and facilitates coordinated spiking or burst firing of CA3 neurons thus reducing the likelihood of recruitment of the same CA3 neurons to distinct ensembles (Csicsvari et al, 2000;de la Prida et al, 2006;Gómez-Ocádiz et al, 2021;Mori et al, 2007;Neubrandt et al, 2017;Sasaki et al, 2018;Torborg et al, 2010). In turn, assemblies of CA3 neurons encoding different contexts entrain activity of downstream ensembles of CA1 principal neurons.…”

An inhibitory circuit-based enhancer of Dyrk1a function reversesDyrk1a-associated impairment in social recognition

“…How does PV mediated perisomatic inhibition of CA3/CA2 contribute to social recognition? Perisomatic inhibition of CA3/CA2 neurons may impose a sparse activity regimen that supports generation of distinct neuronal ensembles in response to an experience (Csicsvari et al, 2000; de la Prida et al, 2006; Gómez-Ocádiz et al, 2021; Guo et al, 2018; Mori et al, 2007; Neubrandt et al, 2017; Sasaki et al, 2018; Torborg et al, 2010; Twarkowski et al, 2022). Consistent with this idea, DGC recruitment of FFI in CA3/CA2 is randomly wired so as to provide blanket inhibition and govern network excitability in CA3 and CA2, rather than couple individual DGC-dependent excitation with inhibition onto distinct populations of pyramidal neurons (Neubrandt et al, 2017).…”

A dentate gyrus-CA3 inhibitory circuit promotes evolution of hippocampal-cortical ensembles during memory consolidation

“…Previous work showed that increasing FFI in DG ‒ CA3 decreases overlap between two context-associated ensembles in CA3 ( Guo et al, 2018 ). We predict that increasing granule cell recruitment of perisomatic inhibition onto CA3 neurons imposes a sparser activity regimen from DG to CA3 thereby reducing the likelihood of recruitment of the same CA3 neurons to distinct ensembles during learning ( Csicsvari et al, 2000 ; de la Prida et al, 2006 ; Gómez-Ocádiz et al, 2021 ; Mori et al, 2007 ; Neubrandt et al, 2017 ; Sasaki et al, 2018 ; Torborg et al, 2010 ). In turn, assemblies of CA3 neurons encoding different contexts entrain activity of downstream ensembles of CA1 principal neurons ( Choi et al, 2018 ; Csicsvari et al, 2000 ; de la Prida et al, 2006 ).…”