Tag Archives: TRN

The brain’s gateway

There have been a few papers lately on the function of the thalamic reticular nucleus (TRN) that characterize it as a filter, a sieve, and a switchboard. The citations and abstracts of 4 of these papers are below. Francis Crick suggested this function for the TRN many years ago but it was not possible until recently to demonstrate it because of the anatomy of the TRN.

The thalamus sits at the center of the brain and is connected to the brain stem and spinal cord below, the cerebral hemispheres above and the basal ganglia to the sides. The thalamus is part of almost all the functional processing loops in the brain. In particular, almost all sensory information enters the cortex from the thalamus, and every corner of the cortex sends signals back to the thalamus. When this traffic, the thalamo-cerebral loops, shut down, so does consciousness.

The TRN is a thin layer of neurons that almost entirely covers the thalamus. Because it is so thin and so deep in the brain, it has been difficult to study. New methods have overcome some of these problems.

In effect all the traffic between the cortex and the thalamus is carried by axons that pass through the TRN and the axons have little branches that make contact with TRN neurons. In other words the TRN gets a smell of all the passing signals – it does not interfere with the axons but just spies on them. The TRN neurons are inhibitory, so when a passing signals activates one of them, it will suppress the neuron in the thalamus that is sending or receiving the signal. This action keeps most activity at a low level. During sleep the thalamo-cerebral loops are effectively turned off and sensory information does not reach the cortex. During attention (and multitasking) the TRN reduces distracting signals but not the attended ones. It also seems to control the type of sleep by controlling types of brain waves in the cortex during sleep. The executive functions of the prefrontal cortex seems to act through the TRN rather than directly on areas of the cortex, to control attention (steer the spotlight of attention).

Here are the abstracts and citations:

Sandra Ahrens, Santiago Jaramillo, Kai Yu, Sanchari Ghosh, Ga-Ram Hwang, Raehum Paik, Cary Lai, Miao He, Z Josh Huang, Bo Li. ErbB4 regulation of a thalamic reticular nucleus circuit for sensory selection. Nature Neuroscience, 2014; DOI: 10.1038/nn.3897

Selective processing of behaviorally relevant sensory inputs against irrelevant ones is a fundamental cognitive function whose impairment has been implicated in major psychiatric disorders. It is known that the thalamic reticular nucleus (TRN) gates sensory information en route to the cortex, but the underlying mechanisms remain unclear. Here we show in mice that deficiency of the Erbb4 gene in somatostatin-expressing TRN neurons markedly alters behaviors that are dependent on sensory selection. Whereas the performance of the Erbb4-deficient mice in identifying targets from distractors was improved, their ability to switch attention between conflicting sensory cues was impaired. These behavioral changes were mediated by an enhanced cortical drive onto the TRN that promotes the TRN-mediated cortical feedback inhibition of thalamic neurons. Our results uncover a previously unknown role of ErbB4 in regulating cortico-TRN-thalamic circuit function. We propose that ErbB4 sets the sensitivity of the TRN to cortical inputs at levels that can support sensory selection while allowing behavioral flexibility.

Ralf D. Wimmer, L. Ian Schmitt, Thomas J. Davidson, Miho Nakajima, Karl Deisseroth, Michael M. Halassa. Thalamic control of sensory selection in divided attention. Nature, 2015; DOI: 10.1038/nature15398

How the brain selects appropriate sensory inputs and suppresses distractors is unknown. Given the well-established role of the prefrontal cortex (PFC) in executive function, its interactions with sensory cortical areas during attention have been hypothesized to control sensory selection. To test this idea and, more generally, dissect the circuits underlying sensory selection, we developed a cross-modal divided-attention task in mice that allowed genetic access to this cognitive process. By optogenetically perturbing PFC function in a temporally precise window, the ability of mice to select appropriately between conflicting visual and auditory stimuli was diminished. Equivalent sensory thalamocortical manipulations showed that behaviour was causally dependent on PFC interactions with the sensory thalamus, not sensory 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 by bidirectional optogenetic manipulations of this subnetwork. Using a combination of electrophysiology and intracellular chloride photometry, we demonstrated that visTRN dynamically controls visual thalamic gain through feedforward inhibition. Our experiments introduce a new subcortical model of sensory selection, in which the PFC biases thalamic reticular subnetworks to control thalamic sensory gain, selecting appropriate inputs for further processing.

Laura D Lewis, Jakob Voigts, Francisco J Flores, Lukas I Schmitt, Matthew A Wilson, Michael M Halassa, Emery N Brown. Thalamic reticular nucleus induces fast and local modulation of arousal state. eLife, October 2015 DOI: 10.7554/eLife.08760

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.

Michael M. Halassa, Zhe Chen, Ralf D. Wimmer, Philip M. Brunetti, Shengli Zhao, Basilis Zikopoulos, Fan Wang, Emery N. Brown, Matthew A. Wilson. State-Dependent Architecture of Thalamic Reticular Subnetworks. Cell, 2014; 158 (4): 808 DOI: 10.1016/j.cell.2014.06.025

Behavioral state is known to influence interactions between thalamus and cortex, which are important for sensation, action, and cognition. The thalamic reticular nucleus (TRN) is hypothesized to regulate thalamo-cortical interactions, but the underlying functional architecture of this process and its state dependence are unknown. By combining the first TRN ensemble recording with psychophysics and connectivity-based optogenetic tagging, we found reticular circuits to be composed of distinct subnetworks. While activity of limbic-projecting TRN neurons positively correlates with arousal, sensory-projecting neurons participate in spindles and show elevated synchrony by slow waves during sleep. Sensory-projecting neurons are suppressed by attentional states, demonstrating that their gating of thalamo-cortical interactions is matched to behavioral state. Bidirectional manipulation of attentional performance was achieved through subnetwork-specific optogenetic stimulation. Together, our findings provide evidence for differential inhibition of thalamic nuclei across brain states, where the TRN separately controls external sensory and internal limbic processing facilitating normal cognitive function.