Pyramidal neurons of the medial Prefrontal Cortex (mPFC) are involved in working memory performance, attention and cognitive control. Here, we investigated changes in GABAergic inhibition of mPFC layer 2/3 pyramidal neurons of adult rats exposed to chronic mild stress (CMS) for eight weeks. This model is recognized to induce behavioral anhedonic-like and cognitive alterations in rats (Henningsen et al., 2009).

Methods: 

In acute slices of rat mPFC, in the prelimbic area, whole-cell patch-clamp recordings of spontaneous IPSCs (sIPSCs), miniature IPSCs (mIPSCs), evoked IPSCs (eIPSCs), tonic GABA_A receptor currents, and GABA_B receptor currents were made from pyramidal cells in control, anhedonic and resilient groups of animals.

Results: 

We found a significant 30% decrease of sIPSC frequency and amplitude in anhedonic rats. Frequency of mIPSCs was 2.2 ± 0.2 Hz (n = 13 cells/4 rats) in control, 2.4 ± 0.5 Hz (n = 13 cells/3 rats) in resilient group and 1.5 ± 0.2 Hz (n = 11 cells/4 rats) in anhedonic rats. Paired-pulse stimulation showed a ratio of eIPSCs in control neurons of 0.67 ± 0.05 (n = 13/5 rats) and 0.94 ± 0.06 (n = 15/7 rats; p < 0.05) in anhedonic rats. Tonic GABAA receptor mediated currents were 33 ± 3 pA (n = 6 cells/5 rats) in control, 28 ± 3 pA (n = 7 cells/4 rats) in resilient and 26 ± 5 pA (n = 6 cells/4 rats) in anhedonic animals. GABA_B mediated potassium currents in mPFC pyramidal neurons in response to the GABA_B agonist baclofen (100 mM, Sigma, UK) were significantly smaller in anhedonic group compared to resilient and control groups, 100 ± 5 pA (n = 6/5 rats; p < 0.001) in anhedonic versus 141 ± 12 pA (n = 8/6 rats) in resilient and 154 ± 8 (n = 8/5 rats) in controls.

Conclusions: 

Our data suggest decreases in both GABA_A and GABA_B receptor mediated inhibition in anhedonic rats. These alterations in GABAergic influence on pyramidal neurons could lead to de-synchronization of the PFC network in depression.