Adolescent Thalamocortical Inhibition Alters Prefrontal Excitation-Inhibition Balance

Abstract

AbstractAdolescent inhibition of thalamo-cortical projections leads to long lasting deficits in prefrontal cortex function and cognition in the adult mouse. While this suggests a role of thalamic activity in prefrontal cortex maturation, it is unclear how inhibition of these projections affects prefrontal network function during adolescence. Here, we used chemogenetic tools to inhibit thalamo-prefrontal projections in the mouse from postnatal day 20-35 and measured synaptic inputs to prefrontal pyramidal neurons by layer (either II/III or V/VI) and projection target twenty-four hours later using slice physiology. We found a decrease in the frequency of excitatory and inhibitory currents in layer II/III nucleus accumbens projecting and layer V/VI mediodorsal thalamus projecting neurons. In contrast, layer V/VI nucleus accumbens projecting neurons showed an increase in the amplitude of excitatory and inhibitory currents. In addition, the frequency of inhibitory currents in contralateral mPFC projecting neurons was also enhanced. Notably, despite these complex changes in individual levels of excitation and inhibition, the overall balance between excitation and inhibition was only changed in cortico-cortical projections. This finding suggests homeostatic regulation occurs within subcortically-but not cross-hemispheric intracortical projecting neurons, increased inhibition of intra-prefrontal connectivity may therefore be particularly important for prefrontal cortex circuit maturation.