Conditioning and pseudoconditioning differently change intrinsic excitability of inhibitory interneurons in the neocortex.

Many studies indicate a broad role of various classes of GABAergic interneurons in the processes related to learning. However, little is known about how the learning process affects intrinsic excitability of specific classes of interneurons in the neocortex. To determine this, we employed a simple model of conditional learning in mice where vibrissae stimulation was used as a conditioned stimulus and a tail shock as an unconditioned one. In vitro whole-cell patch-clamp recordings showed an increase in intrinsic excitability of low-threshold spiking somatostatin-expressing interneurons (SST-INs) in layer 4 (L4) of the somatosensory (barrel) cortex after the conditioning paradigm. In contrast, pseudoconditioning reduced intrinsic excitability of SST-LTS, parvalbumin-expressing interneurons (PV-INs), and vasoactive intestinal polypeptide-expressing interneurons (VIP-INs) with accommodating pattern in L4 of the barrel cortex. In general, increased intrinsic excitability was accompanied by narrowing of action potentials (APs), whereas decreased intrinsic excitability coincided with AP broadening. Altogether, these results show that both conditioning and pseudoconditioning lead to plastic changes in intrinsic excitability of GABAergic interneurons in a cell-specific manner. In this way, changes in intrinsic excitability can be perceived as a common mechanism of learning-induced plasticity in the GABAergic system.

Somatostatin-expressing interneurons modulate neocortical network through GABAb receptors in a synapse-specific manner.

The firing activity of somatostatin-expressing inhibitory neurons (SST-INs) can suppress network activity via both GABAa and GABAb receptors (Rs). Although SST-INs do not receive GABAaR input from other SST-INs, it is possible that SST-IN-released GABA could suppress the activity of SST-INs themselves via GABAbRs, providing a negative feedback loop. Here we characterized the influence of GABAbR modulation on SST-IN activity in layer 2/3 of the somatosensory cortex in mice. We compared this to the effects of GABAbR activation on parvalbumin-expressing interneurons (PV-INs). Using in vitro whole-cell patch clamp recordings, pharmacological and optogenetic manipulations, we found that the firing activity of SST-INs suppresses excitatory drive to themselves via presynaptic GABAbRs. Postsynaptic GABAbRs did not influence SST-IN spontaneous activity or intrinsic excitability. Although GABAbRs at pre- and postsynaptic inputs to PV-INs are modestly activated during cortical network activity in vitro, the spontaneous firing of SST-INs was not the source of GABA driving this GABAbR activation. Thus, SST-IN firing regulates excitatory synaptic strength through presynaptic GABAbRs at connections between pyramidal neurons (Pyr-Pyr) and synapses between pyramidal neurons and SST-INs (Pyr-SST), but not Pyr-PV and PV-Pyr synapses. Our study indicates that two main types of neocortical inhibitory interneurons are differentially modulated by SST-IN-mediated GABA release.