The thalamocortical projection to layer 4 (L4) is thought to be the main route by which sensory organs communicate with cortex. Sensory information is believed to then propagate through the cortical column along the L4→L2/3→L5/6 pathway. We discovered that sensory-evoked responses of L5/6 neurons derive instead from direct thalamocortical synapses. Many L5/6 neurons exhibited sensory-evoked post-synaptic potentials 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, particularly in L5B. Pharmacological inactivation of L4 had no effect on sensory-evoked synaptic input to L5/6 neurons. L4 is thus not an obligatory distribution hub for cortical activity, and thalamus activates two separate, independent “strata” of cortex in parallel.

SUMMARY 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 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. We conclude that global brain states can switch local recurrent networks into different regimes via direct neuromodulation. Our results provide a basis for understanding how sleep/wake cycles alter synaptic integration in cortical neurons.

Decision-making in dynamic environments often involves accumulation of evidence, in which new information is used to update beliefs and select future actions. Using in vivo cellular resolution imaging in voluntarily head-restrained rats, we examined the responses of neurons in frontal and parietal cortices during a pulse-based accumulation of evidence task. Neurons exhibited activity that predicted the animal's upcoming choice, previous choice, and graded responses that reflected the strength of the accumulated evidence. The pulsatile nature of the stimuli enabled characterization of the responses of neurons to a single quantum (pulse) of evidence. Across the population, individual neurons displayed extensive heterogeneity in the dynamics of responses to pulses. The diversity of responses was sufficiently rich to form a temporal basis for accumulated evidence estimated from a latent variable model. These results suggest that heterogeneous, often transient sensory responses distributed across the fronto-parietal cortex may support working memory on behavioral timescales. VIDEO ABSTRACT.

Decision-making behavior is often characterized by substantial variability, but its source remains unclear. We developed a visual accumulation of evidence task designed to quantify sources of noise and to be performed during voluntary head restraint, enabling cellular resolution imaging in future studies. Rats accumulated discrete numbers of flashes presented to the left and right visual hemifields and indicated the side that had the greater number of flashes. Using a signal-detection theory-based model, we found that the standard deviation in their internal estimate of flash number scaled linearly with the number of flashes. This indicates a major source of noise that, surprisingly, is not consistent with the widely used 'drift-diffusion modeling' (DDM) approach but is instead closely related to proposed models of numerical cognition and counting. We speculate that this form of noise could be important in accumulation of evidence tasks generally.DOI: http://dx.doi.org/10.7554/eLife.11308.001

Highlights d A novel task enables application of core behavioral economic approaches in rodents d Like humans, rats exhibit nonlinear utility and probability weighting d Rats also exhibit trial history effects, consistent with ongoing learning d A reinforcement learning model incorporating subjective value accounts for the data