Learning-induced plasticity in the barrel cortex is disrupted by inhibition of layer 4 somatostatin-containing interneurons.

Gaba-ergic neurons are a diverse cell class with extensive influence over cortical processing, but their role in experience-dependent plasticity is not completely understood. Here we addressed the role of cortical somatostatin- (SOM-INs) and vasoactive intestinal polypeptide- (VIP-INs) containing interneurons in a Pavlovian conditioning where stimulation of the vibrissae is used as a conditioned stimulus and tail shock as unconditioned one. This procedure induces a plastic change observed as an enlargement of the cortical functional representation of vibrissae activated during conditioning. Using layer-targeted, cell-selective DREADD transductions, we examined the involvement of SOM-INs and VIP-INs activity in learning-related plastic changes. Under optical recordings, we injected DREADD-expressing vectors into layer IV (L4) barrels or layer II/III (L2/3) areas corresponding to the activated vibrissae. The activity of the interneurons was modulated during all conditioning sessions, and functional 2-deoxyglucose (2DG) maps were obtained 24 h after the last session. In mice with L4 but not L2/3 SOM-INs suppressed during conditioning, the plastic change of whisker representation was absent. The behavioral effect of conditioning was disturbed. Both L4 SOM-INs excitation and L2/3 VIP-INs inhibition during conditioning did not affect the plasticity or the conditioned response. We found the activity of L4 SOM-INs is indispensable in the formation of learning-induced plastic change. We propose that L4 SOM-INs may provide disinhibition by blocking L4 parvalbumin interneurons, allowing a flow of information into upper cortical layers during learning.

Interneurons containing somatostatin are affected by learning-induced cortical plasticity.

The maintenance of neural circuit stability is a dynamic process that requires the plasticity of many cellular and synaptic components. By changing the excitatory/inhibitory balance, inhibitory GABAergic plasticity can regulate excitability, and contribute to neural circuit function and refinement in learning and memory. Increased inhibitory GABAergic neurotransmission has been shown in brain structures involved in the learning process. Previously, we showed that classical conditioning in which tactile stimulation of one row of vibrissae (conditioned stimulus, CS) was paired with a tail shock (unconditioned stimulus, UCS) in adult mice results in the increased density of GABAergic interneurons and increased expression of glutamic acid decarboxylase (GAD)-67 in barrels of the "trained" row cortical representation. In inhibitory neurons of the rat cortex GAD co-localizes with several proteins and peptides. We found previously that the density of the parvalbumin (GAD+/Prv+)-containing subpopulation is not changed after conditioning. In the present study, we examined GABAergic somatostatin (Som)-, calbindin (CB)- and calretinin (CR)-positive interneurons in the cortical representation of "trained" vibrissae after training. Cells showing double immunostaining for GAD/Som, GAD/CR and GAD/CB were counted in the barrels representing vibrissae activated during the training and in control, untouched rows. We found a substantial increase of GAD/Som-containing cells in the trained row representation. No changes in the density of GAD/CR or GAD/CB neurons were observed. These results suggest that Som-containing interneurons are involved in learning-induced changes in the inhibitory cortical network.