The Thalamic Reticular Nucleus in Schizophrenia and Bipolar Disorder: Role of Neurons Expressing Parvalbumin

Abstract

Despite the prevalence and impact on society of Schizophrenia (SZ) and Bipolar Disorder (BD), their precise etiology and pathophysiology remain uncertain. Growing evidence points to a disruption of cortico-thalamo-cortical circuits in these disorders. The involvement of the Thalamic Reticular Nucleus (TRN), a key region necessary for sensory gating and attentional modulation (aspects related to symptoms of SZ and BD), has not been examined in people with these disorders. This is due, in large part, to the difficulty in identifying this structure with current brain imaging techniques, a limitation that can be addressed with postmortem microscopy approaches. We used human postmortem studies to test the hypothesis that neurons expressing parvalbumin (PVB), a main TRN neuronal population, and associated Wisteria floribunda agglutinin-labeled perineuronal nets (WFA/PNNs) are altered in SZ and BD. Our results show that in both SZ and BD there is a marked decrease of neurons expressing PVB and of WFA/PNNs within the TRN, with no effects of duration of illness or age of onset. These results indicate abnormalities of neurons expressing PVB in the TRN of subjects with SZ and BD, and support the hypothesis that deficits in these neurons in the TRN may underlie the neuropathology of these disorders. We put forth that these TRN abnormalities may contribute to disruptions of sleep spindles, focused attention and emotion processing in SZ and BD.