A Cortico-Hippocampal Learning Rule Shapes Inhibitory Microcircuit Activity to Enhance Hippocampal Information Flow

Abstract

Summary How does coordinated activity between distinct brain regions implement a set of learning rules to sculpt information processing in a given neural circuit? Using interneuron cell-type specific optical activation and pharmacogenetic silencing in vitro, we show that temporally precise pairing of direct entorhinal perforant path (PP) and trisynaptic Schaffer collateral (SC) inputs to CA1 pyramidal cells selectively suppresses SC-associated perisomatic inhibition from cholecystokinin (CCK) expressing interneurons. The CCK interneurons provide a surprisingly strong feed-forward inhibitory drive to effectively control the coincident excitation of CA1 pyramidal neurons by convergent inputs. Thus, in-phase cortico-hippocampal activity provides a powerful heterosynaptic learning rule for long-term gating of information flow through the hippocampal excitatory macrocircuit by the silencing of the CCK inhibitory microcircuit.

Theta Phase Segregation of Input-Specific Gamma Patterns in Entorhinal-Hippocampal Networks

“…During the recall phase (center arm) of the T maze task, the CA3 and EC3 inputs may cooperatively increase their influence on CA1 (Montgomery and Buzsáki, 2007; Yamamoto et al, 2014). Properly timed CA3 and EC3 input can also become more effective through suppression of feed-forward inhibition (Buzsáki et al, 1995; Yeckel and Berger, 1990; Leão et al, 2012; Basu et al, 2013) or facilitating mechanisms that can overcome inhibition (Remondes and Schuman, 2002; Jarsky et al, 2005; Takahashi and Magee, 2009). …”

Tasks for inhibitory interneurons in intact brain circuits

“…Feed-forward inhibition thus can reduce the spike responses of principal neurons, by competing with dendritic excitation or reducing output spiking. A recent study suggested that cholecystokinin (CCK) positive basket cells are primarily involved in the feed-forward inhibition of hippocampal CA1 pyramidal cells (Basu et al , 2013). Whether feed-forward inhibition brings about a subtractive or divisive action in the visual cortex is still debated (Atallah et al , 2012; Lee et al , 2012; Wilson et al , 2012; Lee et al , 2014a) and may depend whether the inhibitory target is dendrites or the perisomatic region.…”

Toward a Genetic Dissection of Cortical Circuits in the Mouse

“…In the hippocampus, a subset of cholecystokinin (CCK) positive interneurons in CA1 is recruited by Schaffer collaterals and provide feedforward inhibition to control the coincident excitation of CA1 pyramidal neurons by convergent entorhinal perforant path (PP) and SC inputs. The temporally precise pairing of PP and SC inputs suppresses SC-associated CCK interneurons and provide a hetero-synaptic learning rule for gating information flow through hippocampal circuits (Basu et al, 2013). Together, these studies begin to provide compelling evidence that phenotypically diverse interneurons do not reflect a continuum with no definable class boundary and distinct function (Petilla Interneuron Nomenclature et al, 2008).…”