Subcortical Inputs Governing Cortical Network Activity
Sensory information is represented in cortex by cascades of excitation, the patterns of which are constrained and biased by anatomical connections between neurons. Additionally, in the living animal, functional connectivity is dynamically adjusted by internally generated background activity, which varies by arousal state and behavioral context. Therefore, to understand how excitation propagates through the cortex, it is necessary to characterize the laminar flow of signal propagation as well as spontaneous network activity, which will constrain that propagation. This thesis characterizes the nature and mechanisms of awake cortical network dynamics, as well as the sources of sensory inputs in different cortical layers of the rat somatosensory system. Mammalian brains generate internal activity independent of environmental stimuli. Internally generated states may bring about distinct cortical processing modes. To investigate how brain state impacts cortical circuitry, we recorded intracellularly from the same neurons, under anesthesia and subsequent wakefulness, in the rat barrel cortex. In every cell examined throughout layers 2-6, wakefulness produced a temporal pattern of synaptic inputs differing markedly from those under anesthesia. Recurring periods of synaptic quiescence, prominent under anesthesia, were abolished by wakefulness, which produced instead a persistently depolarized state. This switch in dynamics was unaffected by elimination of afferent synaptic input from thalamus, suggesting that arousal alters cortical dynamics by neuromodulators acting directly on cortex. Indeed, blockade of noradrenergic, but not cholinergic, pathways induced synaptic quiescence during wakefulness. This thesis shows that subcortical inputs from the locus coeruleus-noradrenergic system can switch local recurrent networks into different regimes via direct neuromodulation. Having characterized the nature of wakeful dynamics, I next sought to characterize how sensory information propagates through the cortex. The thalamocortical projection to layer 4 (L4) of primary sensory cortex is thought to be the main route by which information from sensory organs reaches the neocortex. Sensory information is believed to then propagate through the cortical column along the L4→L2/3→L5/6 pathway. This thesis shows that sensory-evoked responses of L5/6 neurons derive from direct thalamocortical synapses, rather than the intracortical pathway. A substantial proportion of L5/6 neurons exhibit sensory-evoked postsynaptic potentials and spikes with the same latencies as L4. Paired in vivo recordings from L5/6 neurons and thalamic neurons revealed significant convergence of direct thalamocortical synapses onto diverse types of infragranular neurons. Pharmacological inactivation of L4 had no effect on sensory-evoked synaptic input to L5/6 neurons, and responsive L5/6 neurons continued to discharge spikes. In contrast, inactivation of thalamus suppressed sensory-evoked responses. This thesis shows that L4 is not an obligatory distribution hub for cortical activity, contrary to long-standing belief, and that thalamus activates two separate, independent "strata" of cortex in parallel.
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