Curtailing Effect of Awakening on Visual Responses of Cortical Neurons by Cholinergic Activation of Inhibitory Circuits

Abstract

Visual responsiveness of cortical neurons changes depending on the brain state. Neural circuit mechanism underlying this change is unclear. By applying the method of in vivo two-photon functional calcium imaging to transgenic rats in which GABAergic neurons express fluorescent protein, we analyzed changes in visual response properties of cortical neurons when animals became awakened from anesthesia. In the awake state, the magnitude and reliability of visual responses of GABAergic neurons increased whereas the decay of responses of excitatory neurons became faster. To test whether the basal forebrain (BF) cholinergic projection is involved in these changes, we analyzed effects of electrical and optogenetic activation of BF on visual responses of mouse cortical neurons with in vivo imaging and whole-cell recordings. Electrical BF stimulation in anesthetized animals induced the same direction of changes in visual responses of both groups of neurons as awakening. Optogenetic activation increased the frequency of visually evoked action potentials in GABAergic neurons but induced the delayed hyperpolarization that ceased the late generation of action potentials in excitatory neurons. Pharmacological analysis in slice preparations revealed that photoactivation-induced depolarization of layer 1 GABAergic neurons was blocked by a nicotinic receptor antagonist, whereas non-fast-spiking layer 2/3 GABAergic neurons was blocked only by the application of both nicotinic and muscarinic receptor antagonists. These results suggest that the effect of awakening is mediated mainly through nicotinic activation of layer 1 GABAergic neurons and mixed nicotinic/muscarinic activation of layer 2/3 non-fast-spiking GABAergic neurons, which together curtails the visual responses of excitatory neurons.

Spinalization and locomotor training differentially affect muscarinic acetylcholine receptor type 2 abutting on α‐motoneurons innervating the ankle extensor and flexor muscles

“…; Kimura et al . ). Physiological and pathological role of M2 receptors located extrasynaptically on MNs is enigmatic, but functional compartmentalization shown for NMDA receptors (Papouin et al .…”

Serotonin 5‐HT1B receptor‐mediated calcium influx‐independent presynaptic inhibition of GABA release onto rat basal forebrain cholinergic neurons

“…In addition, a recent study has demonstrated that cholinergic projection from BF can modulate cortical responses to visual stimulation (Kimura et al ., ), as well as auditory stimulation (Letzkus et al ., ). Therefore, 5‐HT 1B receptor‐mediated inhibition of GABAergic inputs to BF cholinergic neurons could indirectly modulate such sensory processing in the cortex.…”

Illuminating the role of cholinergic signaling in circuits of attention and emotionally salient behaviors

“…The application of optogenetic tools to the analysis of central cholinergic signaling using ChAT-Cre lines in either mice (Kalmbach et al, 2012 ; Huang and Zeng, 2013 ) or rats (Witten et al, 2011 ; see Figure 1 ) allows selective activation and silencing of cholinergic neurons and axonal projections, both in vitro and in vivo . Using this approach, several studies have now shown that ACh signaling occurs through direct, fast synaptic transmission—as well as over longer time scales consistent with more diffuse transmission—in the cortex (Letzkus et al, 2011 ; Arroyo et al, 2012 , 2014 ; Bennett et al, 2012 ; Kimura et al, 2014 ). Activating channelrhodopsin (ChR2) in fibers from the BF elicited a barrage of inhibitory synaptic inputs to layer (L) 2/3 pyramidal cells, which depended on nAChR activation (Arroyo et al, 2012 , 2014 ; Bennett et al, 2012 ; Kimura et al, 2014 ).…”

“…Using this approach, several studies have now shown that ACh signaling occurs through direct, fast synaptic transmission—as well as over longer time scales consistent with more diffuse transmission—in the cortex (Letzkus et al, 2011 ; Arroyo et al, 2012 , 2014 ; Bennett et al, 2012 ; Kimura et al, 2014 ). Activating channelrhodopsin (ChR2) in fibers from the BF elicited a barrage of inhibitory synaptic inputs to layer (L) 2/3 pyramidal cells, which depended on nAChR activation (Arroyo et al, 2012 , 2014 ; Bennett et al, 2012 ; Kimura et al, 2014 ). Pyramidal neurons in L2/3 apparently do not express nAChRs themselves, but L2/3 interneurons do (Poorthuis et al, 2013 ).…”

“…L1 and L2/3 LS neurons exhibited both a fast and a slow response, while L2/3 ChAT bipolar neurons exhibited only a slow response. Activation of L2/3 interneurons by ACh via both nicotinic and muscarinic receptors depressed pyramidal neuron firing thereby curtailing visual responses (Kimura et al, 2014 ). ACh-induced excitatory postsynaptic currents were generated by a mixed population of nAChRs (Arroyo et al, 2012 ).…”