Gamma band activity in the developing parafascicular nucleus ( Pf ) 1

23 The parafascicular nucleus (Pf) receives cholinergic input from the pedunculopontine 24 nucleus, part of the reticular activating system involved in waking and REM sleep, and sends 25 projections to the cortex. We tested the hypothesis that Pf neurons fire maximally at gamma 26 band frequency (30-90 Hz), that this mechanism involves high threshold voltage-dependent 27 P/Qand N-type calcium channels, and that this activity is enhanced by the cholinergic agonist 28 carbachol (CAR). Patch-clamped 9-25 day rat Pf neurons (n=299) manifested a firing frequency 29 plateau at gamma band when maximally activated (31.5±1.5 Hz), showed gamma oscillations 30 when voltage-clamped at holding potentials above -20 mV, and the frequency of the oscillations 31 increased significantly with age (24.6±3.8 Hz vs 51.6±4.4 Hz, p<0.001), but plateaued at 32 gamma frequencies. Cells exposed to CAR showed significantly higher frequencies early in 33 development compared to those without CAR (24.6±3.8 Hz vs 41.7±4.3 Hz, p<0.001), but 34 plateaued with age. The P/Q-type calcium channel blocker ω-Agatoxin-IVA (ω-Aga) blocked 35 gamma oscillations, while the N-type blocker ω-Conotoxin-GVIA (ω-CgTx) only partially 36 decreased the power spectrum amplitude of gamma oscillations. The blocking effect of ω-Aga 37 on P/Q-type currents and ω-CgTx on N-type currents was consistent over age. We conclude 38 that P/Q-, and N-type, calcium channels appear to mediate Pf gamma oscillations during 39 development. We hypothesize that the cholinergic input to the Pf could activate these cells to 40 oscillate at gamma frequency, and perhaps relay these rhythms to cortical areas, thus providing 41 a stable high frequency state for “non-specific” thalamocortical processing. 42