Details

Autor(en) / Beteiligte

• Thankachan, S
• Shukla, C
• McKenna, JT
• McNally, JM
• Zant, JC
• Winston, S
• Brown, RE
• Basheer, R
• McCarley, RW

Titel

0102 BASAL FOREBRAIN PARVALBUMIN NEURONS PROMOTE SHORT-LATENCY AROUSALS AND WAKEFULNESS IN MICE

Ist Teil von

• Sleep (New York, N.Y.), 2017-04, Vol.40 (suppl_1), p.A38-A38

Ort / Verlag

US: Oxford University Press

Erscheinungsjahr

2017

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Abstract Introduction: Cortically-projecting basal forebrain (BF) GABAergic parvalbumin (PV) neurons discharge at a high rate during wakefulness and regulate cortical gamma band (~40 Hz) oscillations associated with feature binding, attention and consciousness (Kim et al., 2015). These neurons are excited by acetylcholine and may mediate the arousal effects of BF cholinergic neurons (Yang et al., 2014; Zant et al., 2016). We hypothesized that input from BF-PV neurons to cortical-PV neurons would mediate a short-latency arousal when optogenetically stimulated since BF-PV neurons project directly onto cortical-PV neurons (Kim et al., 2015). Methods: We injected PV-Cre mice (N=14) with double-floxed adeno-associated viral vectors expressing Channelrhodopsin2 (AAV-ChR2-EYFP) bilaterally into BF. 40Hz optogenetic stimulations (5s/min) of BF-PV neurons (blue laser 473nm, 20mW) were performed from ZT2-8 to evaluate during stimulation: (1) the latency to arousal from NREM-sleep; (2) frequency of NREM-Wake transitions; and (3) time spent in wake, NREM, and REM state. Time-matched mock-stimulation (laser-off) served as baseline (BL) control. The ‘median’ statistic (Mann-Whitney test) comparison was used because of the skewed, non-normal distribution of responses. Post-hoc immunohistochemistry confirmed transduction efficiency/selectivity and optical-fiber targeting within BF. Results: The median latency for NREM-wakefulness transitions was significantly decreased for bilateral stimulation (BL 19.53 ± 1.0s (SEM); Stimulation 3.96 ± 0.7s, p<0.001; N=14). Of all NREM-Wake transitions, the majority of events occurred within 5s from the start of optical stimulation (BL 19.31 ± 1.9%; Stimulation 67.76 ± 4.8%; p<0.05). We observed that bilateral stimulations (N=14) significantly increased the time spent in wakefulness by 14.2 ± 3.4% (p<0.05), whereas NREM sleep decreased (-8.5%±2.5%; p<0.05), with no change in REM sleep. Conclusion: Optogenetic stimulation of BF-PV neurons increased overall wakefulness and decreased the median latency for NREM-Wake arousals. Latencies were shorter than those associated with optogenetic stimulation of BF-cholinergic neurons (median:10.6s, Zant et al., 2016). Thus, our data suggests that BF-PV neuronal excitation causes rapid EEG arousal, likely due to fast cortical disinhibition elicited via direct innervation of the inhibitory interneurons. Support (If Any): VA Merit Awards, I01BX001356 (RWM), I01BX001404 (RB), IK2BX002130 (JMM), I01BX002774, R21-NS079866, R21-NS093000, RO1-MH039683, PO1-HL095491. JTM received partial salary compensation and funding from Merck MISP, but has no conflict of interest with this work.