Synaptic Plasticity and Excitation-Inhibition Balance in the Dentate Gyrus: Insights fromIn VivoRecordings in Neuroligin-1, Neuroligin-2, and Collybistin Knockouts

Abstract

The hippocampal dentate gyrus plays a role in spatial learning and memory and is thought to encode differences between similar environments. The integrity of excitatory and inhibitory transmission and a fine balance between them is essential for efficient processing of information. Therefore, identification and functional characterization of crucial molecular players at excitatory and inhibitory inputs is critical for understanding the dentate gyrus function. In this minireview, we discuss recent studies unraveling molecular mechanisms of excitatory/inhibitory synaptic transmission, long-term synaptic plasticity, and dentate granule cell excitability in the hippocampus of live animals. We focus on the role of three major postsynaptic proteins localized at excitatory (neuroligin-1) and inhibitory synapses (neuroligin-2 and collybistin). In vivo recordings of field potentials have the advantage of characterizing the effects of the loss of these proteins on the input-output function of granule cells embedded in a network with intact connectivity. The lack of neuroligin-1 leads to deficient synaptic plasticity and reduced excitation but normal granule cell output, suggesting unaltered excitation-inhibition ratio. In contrast, the lack of neuroligin-2 and collybistin reduces inhibition resulting in a shift towards excitation of the dentate circuitry.

Collybistin SH3‐protein isoforms are expressed in the rat brain promoting gephyrin and GABA‐A receptor clustering at GABAergic synapses

“…CB‐deficient mice revealed that CB is necessary for the synaptic localization of GABA A Rs and gephyrin in various brain areas particularly hippocampus, amygdala and cerebellum (Papadopoulos et al., 2007, 2008). CB‐deficient mice also have impaired synaptic function in the hippocampus and dentate gyrus and impaired synaptic plasticity (Jedlicka et al., 2009, 2018; Papadopoulos et al., 2007). These results make our hippocampal neuronal cultures highly suitable to address the synaptic role of the CBSH3+ and CBSH3− isoforms by specifically knocking them down with shRNAs.…”

“…Collybistin-deficient mutants show that CB is essential for postsynaptic clustering of GABA A Rs and gephyrin in several brain regions including hippocampus, amygdala and cerebellum, but not in the cerebral cortex and other brain areas (Papadopoulos et al, 2007(Papadopoulos et al, , 2008. CB-deficient mice also have impaired synaptic function in the hippocampus and dentate gyrus (Jedlicka et al, 2009(Jedlicka et al, , 2018Papadopoulos et al, 2007). In spite of these synaptic phenotypes being manifested only in specific brain regions of the CB-deficient mutants, CB mRNA and protein is expressed by neurons through all brain regions, including the cerebral cortex (Kins et al, 2000;Patrizi et al, 2012), http://mouse.brain -map.org/exper iment/ show/70231011.…”

Enhanced LTP of population spikes in the dentate gyrus of mice haploinsufficient for neurobeachin

“…Recordings in intact mice allow the assessment of distinct properties of neuronal network behaviour that are often difficult to replicate in acute slices or cultures, such as the influence of inhibition on firing activity 29 . Earlier studies have reported that inhibitory synapse function was severely compromised in both acute slices and primary neuronal cultures of null-mutant Nbea neurons 4 , 5 , 7 , 8 .…”

Rho GTPase Regulators and Effectors in Autism Spectrum Disorders: Animal Models and Insights for Therapeutics

“…CB KO mice exhibited elevated anxiety levels and impaired spatial memory (Table 2; Supplementary Table S1), and showed reduced GABAergic transmission, increased LTP, and decreased long-term depression (LTD) in hippocampal CA1 region [63]. Two studies using this mouse line investigated electrophysiological characteristics in hippocampal dentate gyrus (DG) region, demonstrating that CB plays an important role in maintaining normal granule cell excitability, GABAergic network inhibition, and synaptic plasticity [64,65].…”