Scientific Understanding of Consciousness
Thalamic Control of Sensory Selection and Divided Attention
Nature 526, 705–709 (29 October 2015)
Thalamic control of sensory selection in divided attention
Ralf D. Wimmer, et.al.
Department of Bioengineering, Stanford University, Stanford, California 94305, USA
Cracking the Neural Code Program, Stanford University, Stanford, California 94305, USA
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, USA
Department of Psychiatry, New York University Langone Medical Center, New York, New York 10016, USA
Center for Neural Science, New York University, New York, New York 10003, USA
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.
Given the known role of PFC in top-down control of sensory processing and that our psychophysical measurements revealed top-down engagement in the cross-modal task, we asked whether cross-modal performance was PFC dependent. We targeted the prelimbic cortex because of its known homology to primate dorsolateral PFC. We used the VGAT-ChR2 mouse to perturb PFC function in a temporally precise manner. In this mouse, the light-activated ion channel channelrhodopsin-2 (ChR2) is expressed under the vesicular GABA (γ-aminobutyric acid) transporter promoter (VGAT). Optogenetic drive in this mouse is known to exert intensity- and duration-dependent inhibition of excitatory neural activity. Using this approach, we observed behavioural disruption only when the PFC activity was perturbed during stimulus anticipation (n = 4 mice). This effect was dependent on the cross-modal nature of the task, as perturbing PFC activity in a visual-only task had no effect on performance regardless of task difficulty (n = 3 mice, ≥246 trials per condition).
Seminal studies have shown the thalamus to be more than a cortical relay. By providing a mechanistic circuit dissection of thalamic involvement in divided attention, we extend these studies in two directions. First, our findings in mice show the generality of thalamic modulation of attention across mammalian brains. Second, we provide a first description, with causal circuit dependence, of how prefrontal top-down control changes thalamic inhibitory dynamics to modulate sensory gain. The specific involvement of prelimbic cortex in this behaviour, which we further demonstrate through combined optogenetics and chloride photometry, does not eliminate the possibility that the OFC and the ACC may be engaged in other types of top-down control, potentially via cortico-cortical interactions. In addition to regulating sensory gain, prelimbic control of thalamic inhibition may regulate the degree by which relay nuclei participate in large-scale functional interactions.
The ability to directly measure [Cl–]i dynamics provided access to a critical biological variable: GABAA-mediated synaptic inhibition. Although photometry has already been introduced into neuroscience for measurement of [Ca2+]i in cell bodies and terminals, FRET-based chloride photometry has not been performed previously. In this study, developing chloride photometry was essential for establishing a direct physiological link between visTRN and LGN spiking.
Thirty years ago, Francis Crick proposed that the TRN functions as a ‘searchlight’, directing the internal spotlight of attention to thalamocortical circuits that process ongoing behavioural demands. Owing to technical limitations, this transformative model has been difficult to test, particularly under conditions where the attentional spotlight shifts. Our study combined novel and established technology to provide mechanistic details for Crick’s ‘searchlight hypothesis’, thereby contributing to understanding the circuit mechanisms of sensory selection.
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