Cholinergic modulation of CRH and non-CRH neurons in Barrington's nucleus of the mouse

Cholinergic modulation of CRH and non-CRH neurons in Barrington's nucleus of the mouse. Corticotropin-releasing hormone (CRH) is expressed in Barrington's nucleus (BarN), which plays an essential role in the regulation of micturition. To control the neural activities of BarN, glutamatergic and GABAergic inputs from multiple sources have been demonstrated; however, it is not clear how modulatory neurotransmitters affect the activity of BarN neurons. We have employed knock-in mice, CRH-expressing neurons of which are labeled with a modified yellow fluorescent protein (Venus). Using whole cell patch-clamp recordings, we examined the responses of Venus-expressing (putative CRH-expressing) neurons in BarN (BarCRH), as well as non-CRHexpressing neurons (BarCRH-negative), following bath application of cholinergic agonists. According to the present study, the activity of BarCRH neurons could be modulated by dual cholinergic mechanisms. First, they are inhibited by a muscarinic receptor-mediated mechanism, most likely through the M2 subclass of muscarinic receptors. Second, BarCRH neurons are excited by a nicotinic receptor-mediated mechanism. BarCRH-negative neurons also responded to cholinergic agents. Choline transporter-immunoreactive nerve terminals were observed in close proximity to the neurites, as well as the somata of BarCRH. The present results suggest that BarN neurons are capable of responding to cholinergic input. NEW & NOTEWORTHY This study investigates the effects of bath-applied cholinergic agonists on Barrington's nucleus (BarN) neurons in vitro. They were either excitatory, through nicotinic receptors, or inhibitory, through muscarinic receptors. Putative corticotropin-releasing hormone (CRH)-expressing neurons in BarN, as well as putative non-CRH-expressing neurons, responded to cholinergic agonists.