RT Journal Article
SR Electronic
T1 Discharge and Role of GABA Pontomesencephalic Neurons in Cortical Activity and Sleep-Wake States Examined by Optogenetics and Juxtacellular Recordings in Mice
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP JN-RM-2875-19
DO 10.1523/JNEUROSCI.2875-19.2020
A1 Youssouf Cissé
A1 Masaru Ishibashi
A1 Josefa Jost
A1 Hanieh Toossi
A1 Lynda Mainville
A1 Antoine Adamantidis
A1 Christopher S. Leonard
A1 Barbara E. Jones
YR 2020
UL http://www.jneurosci.org/content/early/2020/06/23/JNEUROSCI.2875-19.2020.abstract
AB The cholinergic neurons in the pontomesencephalic tegmentum have been shown to discharge in association with and promote cortical activation during active or attentive waking (aW) and paradoxical or rapid eye movement sleep (PS or REMS). However, GABA neurons lie intermingled with the cholinergic neurons and may contribute to or oppose this activity and role. Here we investigated in vitro and in vivo the properties, activities and role of GABA neurons within the laterodorsal tegmental and sublaterodorsal tegmental nuclei (LDT/SubLDT) using male and female transgenic mice expressing channelrhodopsin-2 (ChR2)-enhanced yellow fluorescent protein (EYFP) in vesicular GABA transporter (VGAT) expressing neurons. Presumed (p) GABA neurons were identified by response to photostimulation and verified by immunohistochemical staining following juxtacellular labeling in vivo. pGABA neurons were found to be fast firing neurons with the capacity to burst when depolarized from a hyperpolarized membrane potential. When stimulated in vivo in urethane-anesthetized or unanesthetized mice, the pGABA neurons fired repetitively at relatively fast rates (∼40 Hz) during a continuous light pulse or phasically in bursts (>100 Hz) when driven by rhythmic light pulses at theta (4 or 8 Hz) frequencies. pNonGABA, which likely included cholinergic, neurons were inhibited during each light pulse to discharge rhythmically in antiphase to the pGABA neurons. The reciprocal rhythmic bursting by the pGABA and pNonGABA neurons drove rhythmic theta activity in the EEG. Such phasic bursting by GABA neurons also occurred in wild type mice in association with theta activity during aW and PS.SignificanceNeurons in the pontomesencephalic tegmentum, particularly cholinergic neurons, play an important role in cortical activation, which occurs during active or attentive waking (aW) and paradoxical or rapid eye movement sleep (PS or REMS). Yet the cholinergic neurons lie intermingled with GABA neurons which could play a similar or opposing role. Optogenetic stimulation and recording of these GABA neurons in mice revealed that they can discharge in rhythmic bursts at theta frequencies and drive theta activity in limbic cortex. Such phasic burst firing also occurs during natural aW and PS in association with theta activity and could serve to enhance sensory-motor processing and memory consolidation during these states.