Multiplexed changes in synaptic transmission underlie stress-induced reduction of persistent firing in the parietal cortex.

Repeated exposure to stress disrupts cognitive processes, including attention and working memory. A key mechanism supporting these functions is the ability of neurons to sustain action potential firing, even after a stimulus is no longer present. How stress impacts this persistent neuronal activity is currently unknown. We found that repeated exposure to multiple concurrent stressors during adolescence (aRMS) impedes the ability of layer 5 pyramidal neurons (L5 PNs) in the posterior parietal cortex (PPC) to produce persistent firing. To determine the mechanisms underlying this effect, we complemented computational modelling with whole-cell patch clamp electrophysiology in acute brain slices from male mice. Our model predicted that altered intrinsic excitability, reduced local connectivity, diminished glutamatergic transmission, or enhanced inhibition could explain diminished persistent activity. In Highlights: Stress exposure impairs persistent firing in the posterior parietal cortex.GABAergic inhibition is enhanced following stress.Stress alters excitatory transmission between layer 5 pyramidal cells.Combined changes in inhibition and excitation impact persistent firing.