Basal Forebrain Gating by Somatostatin Neurons Drives Prefrontal Cortical Activity

Abstract

The basal forebrain provides modulatory input to the cortex regulating brain states and cognitive processing. Somatostatin-expressing neurons constitute a heterogeneous GABAergic population known to functionally inhibit basal forebrain cortically projecting cells thus favoring sleep and cortical synchronization. However, it remains unclear if somatostatin cells can regulate population activity patterns in the basal forebrain and modulate cortical dynamics. Here, we demonstrate that somatostatin neurons regulate the corticopetal synaptic output of the basal forebrain impinging on cortical activity and behavior. Optogenetic inactivation of somatostatin neurons in vivo rapidly modified neural activity in the basal forebrain, with the consequent enhancement and desynchronization of activity in the prefrontal cortex, reflected in both neuronal spiking and network oscillations. Cortical activation was partially dependent on cholinergic transmission, suppressing slow waves and potentiating gamma oscillations. In addition, recruitment dynamics was cell type-specific, with interneurons showing similar temporal profiles, but stronger responses than pyramidal cells. Finally, optogenetic stimulation of quiescent animals during resting periods prompted locomotor activity, suggesting generalized cortical activation and increased arousal. Altogether, we provide physiological and behavioral evidence indicating that somatostatin neurons are pivotal in gating the synaptic output of the basal forebrain, thus indirectly controlling cortical operations via both cholinergic and non-cholinergic mechanisms.

Optogenetic Stimulation of Basal Forebrain Parvalbumin Neurons Activates the Default Mode Network and Associated Behaviors

“…However, we consider that the enhancement of quiet wakefulness triggered by DBS may be due to the activation of GABAergic BF circuits. This is consistent with observations in the BF nucleus ventral pallidum, where optogenetic inhibition of SST GABAergic neurons triggers transitions from quiet wakefulness to exploratory behavior as well as enhances running speed (Espinosa et al, 2019a(Espinosa et al, , 2019b. Available evidence thus points to an important role for BF GABAergic circuits in triggering DMN-type behaviors, with grooming and quiet wakefulness possibly involving preferential recruitment of PV and SST GABAergic populations.…”

Effect of basal forebrain somatostatin and parvalbumin neurons in propofol and isoflurane anesthesia

“…Numerous evidences indicated that GABA SOM neurons contain diverse regional populations and functions in the BF. GABA SOM neurons in VP of BF regulate local gamma oscillations to drive prefrontal cortical activity 39,40 . In sleep–wake cycle, BF GABA SOM neurons exert a sleep promoting effect, 10 and the synthetic SOM analog, octreotide, can either suppress NREM sleep or increase REM sleep 41,42 .…”

Cholinergic Modulation of the Default Mode Like Network in Rats

“…In humans, gamma-band activity in DMN areas is elevated during periods of quiet wakefulness and is transiently suppressed during the performance of cognitive tasks ( Miller et al., 2009 ; Ossandon et al., 2011 ). It has been suggested that GABAergic cells, in particular somatostatin-expressing cells, or the glutamatergic cells in the BFB mediate the generation and coordination of these gamma oscillations ( Espinosa et al., 2019a , 2019b ; Yang et al., 2017 ). In our study, analysis of the low-frequency fluctuations in the BOLD signal revealed decreased FC and resting-state neural activity in cortical DMLN region upon stimulation of BFB cholinergic neurons.…”

“…Moreover, ACh enhances visual processing by inducing cortical decorrelation and desynchronization in sensory cortices, which increases the signal to noise ratio ( Chen et al., 2015 ; Nguyen et al., 2015 ; Pinto et al., 2013 ). Moreover, the BFB has been implicated in cortical network switching between brain states by exerting direct and/or indirect control to the prefrontal cortex ( Espinosa et al., 2019b ; Li et al., 2015 ).…”