题目：Optogenetic dissection of the neurons in the basal forebrain

报告人：Tae Kim , Ph.D.

时间：2016年06月01日 星期三 13:00-14:00

地点： 北大王克桢楼11层1113会议室

Abstract: The basal forebrain (BF) is a final node of arousal pathway from brain stem to cortex. Understanding the function of the basal forebrain (BF) poses a challenge due to the intermingled presence of cholinergic, GABAergic, and glutamatergic neurons. All three BF neuronal subtypes project to the cortex and are implicated in cortical function and sleep-wake control. Optogenetic stimulation of parvalbumin (PV)-positive neurons in BF enhances cortical gamma band oscillations in the cortex. On the other hand optogenetic inhibition of BF PV neurons reduced GBO generated by auditory steady state response (ASSR). Therefore, we concluded that BF PV neurons control GBO. These results are surprising and novel in indicating that this presumptively inhibitory BF PV input controls cortical GBO, likely by synchronizing the activity of cortical PV interneurons. BF PV neurons may represent a previously unidentified therapeutic target to treat disorders involving abnormal GBO, such as schizophrenia.
On the other hand, recent studies using optogenetics have shown that "selective" stimulation of BF cholinergic neurons increases transitions between NREM sleep and wakefulness, implicating cholinergic projections to cortex in wake promotion. However, the interpretation of these optogenetic experiments is complicated by interactions that may occur within the BF. For instance, a recent in vitro study from our group found that cholinergic neurons strongly excite neighboring PV/GABAergic neurons (Yang et al., 2014). Thus, the wake-promoting effect of optogenetic stimulation of BF cholinergic neurons could be mediated by local excitation of GABA/PV or other non-cholinergic BF neurons. Using a newly designed "opto-dialysis" probe to couple selective optical stimulation with simultaneous in vivo microdialysis, we demonstrated that optical stimulation of cholinergic neurons locally increased acetylcholine levels and increased wakefulness in mice. The wake-promoting effect caused by cholinergic stimulation was abolished by simultaneous reverse microdialysis of cholinergic receptor antagonists into BF. We found that cholinergic stimulation in the BF promotes wakefulness through local release of acetylcholine in BF and susquent activation of cortically projecting, non-cholinergic neurons, including the GABAergic/PV neurons.