To determine the role of LRIPs in learning, the authors pharmacogenetically silenced these projections in the dorsal CA1 of mice during the training phases of two learning tasks. In a contextual fear-conditioning task, LRIP silencing did not affect the ability of the animals to learn the fear response to the trained context; however, LRIP-silenced animals showed increased fear-related behaviour in a non-trained context, suggesting inappropriate fear learning. In a novel-object recognition task, both the LRIP-silenced and control groups showed memory for the familiar object, as indicated by increased time spent exploring the novel object. However, the difference in the amount of time spent exploring the familiar versus the new object (as a proportion of total exploring time) was reduced in LRIP-silenced mice compared with controls. These data suggest that LRIPs are necessary for memory specificity.
To investigate the role of LRIPs in the hippocampal network, the authors took electrophysiological recordings from a set of GABAergic cholecystokinin-expressing interneurons (CCKINs) in the mouse hippocampus that receive SC excitatory inputs and drive feedforward inhibition on to CA1 pyramidal neuron dendrites. Electrical stimulation of mixed excitatory and inhibitory EC axons induced a small excitatory postsynaptic potential (EPSP) that was dominated by a large hyperpolarization (which peaked at ∼20 ms after stimulation); pharmacogenetic silencing of LRIPs ablated the hyperpolarizing component of this response. EC activation 20 ms before SC stimulation suppressed the ability of SC activation to elicit CCKIN spikes; importantly, silencing LRIPs prevented this spike reduction. Thus, precisely timed LRIP activity can suppress SC input-induced CCKIN spikes.
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