Parvalbumin-positive CA1 interneurons are required for spatial working but not for reference memory

Abstract

Parvalbumin-positive GABAergic interneurons in cortical circuits are hypothesized to control cognitive function. To test this idea directly, we functionally removed parvalbumin-positive interneurons selectively from hippocampal CA1 in mice. We found that parvalbumin-positive interneurons are dispensable for spatial reference, but are essential for spatial working memory.

Hippocampal Neural Disinhibition Causes Attentional and Memory Deficits

“…Our finding, highlighting the importance of GABAergic inhibition for hippocampusdependent memory performance, converges with recent studies in mice reporting learning-related increase of hippocampal inhibitory synapses (Ruediger et al 2012) and impaired memory performance following disruption of hippocampal GABA neuron function by molecular-, opto-or pharmacogenetic approaches (Prut et al 2010;Murray et al 2011;Andrews-Zwilling et al 2012;Caputi et al 2012;Donato et al 2013;Gilani et al 2014;Lovett-Barron et al 2014;Engin et al 2015;Lee et al 2016). Moreover, our findings support recent studies in humans and rodent models linking hippocampal overactivity and hyperexcitability to age-related memory deficits (Koh et al 2010;Bakker et al 2012;Davis et al 2014) and are consistent with the correlation of hippocampal overactivity with memory deficits in schizophrenia (Tregellas et al 2014).…”

“…This has recently been established for prefrontal GABA dysfunction (Gruber et al 2010;Enomoto et al 2011;Paine et al 2011;Pehrson et al 2013;Pezze et al 2014;Paine et al 2015;Tse et al 2015), and there is also evidence linking hippocampal neural disinhibition and overactivity to impaired hippocampus-dependent memory performance (Koh et al 2010;Murray et al 2011;Andrews-Zwilling et al 2012;Bakker et al 2012 ;Caputi et al 2012;Gilani et al 2014;Lovett-Barron et al 2014). Moreover, regional disinhibition, by causing aberrant drive of projections, may disrupt neural activity and cognitive processing in distal sites.…”

Pathological and Pathophysiological Alterations in Temporal Lobe Structures After Mild Traumatic Brain Injury

“…Likewise, we propose that impaired inhibition in the CAl region of the hippocampus may be the underlying cause of memory deficits following mTBI. Loss of parvalbumin-positive interneurons in the CAl regions has been previously associated with memory deficits (207), which is consistent with our findings.…”

Cracking Down on Inhibition: Selective Removal of GABAergic Interneurons from Hippocampal Networks

“…The coordinated interplay of structurally and functionally diverse interneurons in the hippocampus is essential for the dynamic processing of information and allows adaptive experience-dependent modifications to network connectivity (Davies et al, 1998;Bartos et al, 2007;Buzsáki et al, 2007;Cardin et al, 2009;Murray et al, 2011). The molecular diversity of pallial GABAergic interneurons is transcriptionally encoded to define their migratory routes, neurochemical make-up and network contributions (Pleasure et al, 2000;Anderson et al, 2002;Tricoire et al, 2011).…”