State-dependent modulation of subthreshold activity in mouse visual cortex
- Decades of extracellular recording in primate, cat and rodent cortex have established that an animal's behavioral state profoundly modulates the spiking response of sensory cortical neurons to external stimuli. Attention and arousal have been shown to affect not only neuronal responsiveness but also psychophysical thresholds, suggesting a direct link between the cortical sensory representation and perception. However, despite this tremendous progress, the cellular mechanisms by which behavioral states modulate the spiking of cortical neurons remain poorly understood. Here I describe two approaches aimed at understanding how the subthreshold activity of cortical cells is modulated across behavioral states. First, I discuss an in vitro study characterizing the ascending basal forebrain cholinergic system, one of the main neuromodulatory systems in the mammalian brain. Cholinergic cells in the basal forebrain project throughout the cortex and are thought to play an important role in state-dependent modulation of cortical activity. By optogenetically labeling and stimulating cholinergic axons in cortical slices, we were able to characterize 1) what cortical cell types are targeted by cholinergic axons, 2) the relevant time course over which endogenous acetylcholine (ACh) release acts on target cells, and 3) the synaptic properties of cholinergic axons in cortex. We found that cholinergic axons target specific subtypes of cortical interneurons. Moreover, we found clear evidence for classical synaptic transmission between cholinergic release sites and specific interneuron classes, challenging the predominant view that the cholinergic system works primarily by nonsynaptic transmission. Next, to better understand how the subthreshold activity of cortical cells is modulated in the intact brain, we performed intracellular recordings from the visual cortex of awake, head-fixed mice. We showed that the membrane potential of neurons in superficial layers is highly variable during quiet wakefulness and that this variability is quenched when the animal moves. In addition, we found that responses to visual stimulation are larger and more reliable during locomotion, which, together with the decrease in baseline variability, drastically improves the signal to noise ratio. Moreover, by recording from pairs of neurons simultaneously, we showed that the membrane potentials of neighboring cells is highly correlated during quiet wakefulness, but that this correlation subsides during active states. Finally, we demonstrated that neurons in the deep cortical layers display similar state-dependent membrane potential dynamics and that correlated membrane potential fluctuations in superficial cells may originate in deep layers.
|Type of resource
|electronic; electronic resource; remote
|1 online resource.
|Stanford University, Neurosciences Program.
|Knudsen, Eric I
|Knudsen, Eric I
|Statement of responsibility
|Submitted to the Program in Neurosciences.
|Thesis (Ph.D.)--Stanford University, 2015.
- © 2015 by Corbett Clark Bennett
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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