While interactions between the thalamus and cortex are critical for cognitive function1–3, the exact contribution of the thalamus to these interactions is often unclear. Recent studies have shown diverse connectivity patterns across the thalamus 4,5, but whether this diversity translates to thalamic functions beyond relaying information to or between cortical regions6 is unknown. Here, by investigating prefrontal cortical (PFC) representation of two rules used to guide attention, we find that the mediodorsal thalamus (MD) sustains these representations without relaying categorical information. Specifically, MD input amplifies local PFC connectivity, enabling rule-specific neural sequences to emerge and thereby maintain rule representations. Consistent with this notion, broadly enhancing PFC excitability diminishes rule specificity and behavioral performance, while enhancing MD excitability improves both. Overall, our results define a previously unknown principle in neuroscience; thalamic control of functional cortical connectivity. This function indicates that the thalamus plays much more central roles in cognition than previously thought.

How the brain selects appropriate sensory inputs and suppresses distractors is a central unsolved mystery in neuroscience. Given the well-established role of prefrontal cortex (PFC) in executive function1, its interactions with sensory cortical areas during attention have been hypothesized to control sensory selection2–5. To test this idea and more generally dissect the circuits underlying sensory selection, we developed a cross-modal divided attention task in mice enabling genetic access to this cognitive process. By optogenetically perturbing PFC function in a temporally-precise window, the ability of mice to appropriately select between conflicting visual and auditory stimuli was diminished. Surprisingly, equivalent sensory thalamo-cortical manipulations showed that behavior was causally dependent on PFC interactions with sensory thalamus, not cortex. Consistent with this notion, we found neurons of the visual thalamic reticular nucleus (visTRN) to exhibit PFC-dependent changes in firing rate predictive of the modality selected. visTRN activity was causal to performance as confirmed via subnetwork-specific bi-directional optogenetic manipulations. Through a combination of electrophysiology and intracellular chloride photometry, we demonstrated that visTRN dynamically controls visual thalamic gain through feedforward inhibition. Combined, our experiments introduce a new subcortical model of sensory selection, where prefrontal cortex biases thalamic reticular subnetworks to control thalamic sensory gain, selecting appropriate inputs for further processing.

The brain remains one of the most important but least understood tissues in our body, in part because of its complexity as well as the limitations associated with in vivo studies. Although simpler tissues have yielded to the emerging tools for in vitro 3D tissue cultures, functional brain-like tissues have not. We report the construction of complex functional 3D brain-like cortical tissue, maintained for months in vitro, formed from primary cortical neurons in modular 3D compartmentalized architectures with electrophysiological function. We show that, on injury, this brain-like tissue responds in vitro with biochemical and electrophysiological outcomes that mimic observations in vivo. This modular 3D brain-like tissue is capable of real-time nondestructive assessments, offering previously unidentified directions for studies of brain homeostasis and injury.electrophysiology | connectivity | silk | scaffold | traumatic brain injury

During low arousal states such as drowsiness and sleep, cortical neurons exhibit rhythmic slow wave activity associated with periods of neuronal silence. Slow waves are locally regulated, and local slow wave dynamics are important for memory, cognition, and behaviour. While several brainstem structures for controlling global sleep states have now been well characterized, a mechanism underlying fast and local modulation of cortical slow waves has not been identified. Here, using optogenetics and whole cortex electrophysiology, we show that local tonic activation of thalamic reticular nucleus (TRN) rapidly induces slow wave activity in a spatially restricted region of cortex. These slow waves resemble those seen in sleep, as cortical units undergo periods of silence phase-locked to the slow wave. Furthermore, animals exhibit behavioural changes consistent with a decrease in arousal state during TRN stimulation. We conclude that TRN can induce rapid modulation of local cortical state.DOI: http://dx.doi.org/10.7554/eLife.08760.001