Acetylcholine functionally reorganizes neocortical microcircuits

Abstract

Runfeldt MJ, Sadovsky AJ, MacLean JN. Acetylcholine functionally reorganizes neocortical microcircuits. J Neurophysiol 112: 1205-1216, 2014. First published May 28, 2014 doi:10.1152/jn.00071.2014.-Sensory information is processed and transmitted through the synaptic structure of local cortical circuits, but it is unclear how modulation of this architecture influences the cortical representation of sensory stimuli. Acetylcholine (ACh) promotes attention and arousal and is thought to increase the signal-to-noise ratio of sensory input in primary sensory cortices. Using high-speed two-photon calcium imaging in a thalamocortical somatosensory slice preparation, we recorded action potential activity of up to 900 neurons simultaneously and compared local cortical circuit activations with and without bath presence of ACh. We found that ACh reduced weak pairwise relationships and excluded neurons that were already unreliable during circuit activity. Using action potential activity from the imaged population, we generated functional wiring diagrams based on the statistical dependencies of activity between neurons. ACh pruned weak functional connections from spontaneous circuit activations and yielded a more modular and hierarchical circuit structure, which biased activity to flow in a more feedforward fashion. Neurons that were active in response to thalamic input had reduced pairwise dependencies overall, but strong correlations were conserved. This coincided with a prolonged period during which neurons showed temporally precise responses to thalamic input. Our results demonstrate that ACh reorganizes functional circuit structure in a manner that may enhance the integration and discriminability of thalamic afferent input within local neocortical circuitry.

Putative Microcircuit-Level Substrates for Attention Are Disrupted in Mouse Models of Autism

“…Here, by studying isolated microcircuits within brain slices, we demonstrate unequivocally that the decorrelations observed in vivo can emerge as a result of cholinergic modulation acting directly on microcircuits. (Interestingly, whereas we studied ongoing patterns of spontaneous network activity similar to those believed to mediate attentional effects in vivo , another recent in vitro study (4) showed that acetylcholine decorrelates the latency to the first spike in somatosensory neurons responding to thalamic input).…”

“…Until recently, a major barrier to identifying such circuit-level abnormalities has been recording from large numbers of neurons simultaneously. However, advances in imaging and electrophysiological techniques have made it possible to characterize patterns of circuit-level activity by, for example, calculating correlations between neurons (3, 4). Despite these advances, cognitive processes are associated with complex neural dynamics embedded within a high dimensional state space.…”

The neuroscience of cognitive-motivational styles: Sign- and goal-trackers as animal models.

“…Using diverse research approaches ranging from assessing effects of selective lesions, amperometric measures of the fast, phasic, or transient component of cholinergic neurotransmission, microdialysis measures of levels of cholinergic neuromodulation, neurophysiological recordings, and optogenetic generation and attenuation of fast cholinergic transients in performing rodents, the basal forebrain cholinergic projection system to the cortex has been shown to mediate, necessarily, the incorporation of cues into cortical circuitry, thereby allowing such cues to control behavior (Avery, Dutt, & Krichmar, 2014; Goard & Dan, 2009; Gritton et al, 2016; Howe et al, 2013; Howe et al, 2017; McGaughy et al, 1996; Parikh, Kozak, Martinez, & Sarter, 2007; Pinto et al, 2013; Runfeldt, Sadovsky, & MacLean, 2014; Sarter, Howe, & Gritton, 2015; Sarter, Lustig, Berry, et al, 2016; Sarter, Lustig, Howe, Gritton, & Berry, 2014). Furthermore, levels of cholinergic neuromodulation influence the likelihood and the amplitudes of cholinergic transients that cause the detection of cues in attentional contexts (for a circuitry model underlying this interaction see Hasselmo & Sarter, 2011).…”

Spontaneous activations follow a common developmental course across primary sensory areas in mouse neocortex

“…These spontaneous activations are blocked by inhibitors of excitatory neurotransmitters (Cossart et al 2005;Runfeldt et al 2014) and are not recapitulated by a rate-matched null model of independent Poisson neurons (Chambers and MacLean 2015).…”