Search

As the tools to simultaneously record electrophysiological signals from large numbers of neurons within and across brain regions become increasingly available, this opens up for the first time the possibility of establishing the details of causal relationships between monosynaptically connected neurons and the patterns of neural activation that underlie perception and behavior. Although recorded activity across synaptically connected neurons has served as the cornerstone for much of what we know about synaptic transmission and plasticity, this has largely been relegated to ex vivo preparations that enable precise targeting under relatively well-controlled conditions. Analogous studies in vivo, where image-guided targeting is often not yet possible, rely on indirect, data-driven measures, and as a result such studies have been sparse and the dependence upon important experimental parameters has not been well studied. Here, using in vivo extracellular single-unit recordings in the topographically aligned rodent thalamocortical pathway, we sought to establish a general experimental and computational framework for inferring synaptic connectivity. Specifically, attacking this problem within a statistical signal detection framework utilizing experimentally recorded data in the ventral-posterior medial (VPm) region of the thalamus and the homologous region in layer 4 of primary somatosensory cortex (S1) revealed a trade-off between network activity levels needed for the data-driven inference and synchronization of nearby neurons within the population that results in masking of synaptic relationships. Here, we provide a framework for establishing connectivity in multisite, multielectrode recordings based on statistical inference, setting the stage for large-scale assessment of synaptic connectivity within and across brain structures. NEW & NOTEWORTHY Despite the fact that all brain function relies on the long-range transfer of information across different regions, the tools enabling us to measure connectivity across brain structures are lacking. Here, we provide a statistical framework for identifying and assessing potential monosynaptic connectivity across neuronal circuits from population spiking activity that generalizes to large-scale recording technologies that will help us to better understand the signaling within networks that underlies perception and behavior.

Sensory signals from the outside world are transduced at the periphery, passing through thalamus before reaching cortex, ultimately giving rise to the sensory representations that enable us to perceive the world. The thalamocortical circuit is particularly sensitive to the temporal precision of thalamic spiking due to highly convergent synaptic connectivity. Thalamic neurons can exhibit burst and tonic modes of firing that strongly influence timing within the thalamus. The impact of these changes in thalamic state on sensory encoding in the cortex, however, remains unclear. Here, we investigated the role of thalamic state on timing in the thalamocortical circuit of the vibrissa pathway in the anesthetized rat. We optogenetically hyperpolarized thalamus while recording single unit activity in both thalamus and cortex. Tonic spike-triggered analysis revealed temporally precise thalamic spiking that was locked to weak white-noise sensory stimuli, whereas thalamic burst spiking was associated with a loss in stimulus-locked temporal precision. These thalamic state-dependent changes propagated to cortex such that the cortical timing precision was diminished during the hyperpolarized (burst biased) thalamic state. Although still sensory driven, the cortical neurons became significantly less precisely locked to the weak white-noise stimulus. The results here suggests a state-dependent differential regulation of spike timing precision in the thalamus that could gate what signals are ultimately propagated to cortex. NEW & NOTEWORTHY The majority of sensory signals are transmitted through the thalamus. There is growing evidence of complex thalamic gating through coordinated firing modes that have a strong impact on cortical sensory representations. Optogenetic hyperpolarization of thalamus pushed it into burst firing that disrupted precise time-locked sensory signaling, with a direct impact on the downstream cortical encoding, setting the stage for a timing-based thalamic gate of sensory signaling.

Sensory stimulation drives complex interactions across neural circuits as information is encoded and then transmitted from one brain region to the next. In the highly interconnected thalamocortical circuit, these complex interactions elicit repeatable neural dynamics in response to temporal patterns of stimuli that provide insight into the circuit properties that generated them. Here, using a combination of in vivo voltage-sensitive dye (VSD) imaging of cortex, single-unit recording in thalamus, and optogenetics to manipulate thalamic state in the rodent vibrissa pathway, we probed the thalamocortical circuit with simple temporal patterns of stimuli delivered either to the whiskers on the face (sensory stimulation) or to the thalamus directly via electrical or optogenetic inputs (artificial stimulation). VSD imaging of cortex in response to whisker stimulation revealed classical suppressive dynamics, while artificial stimulation of thalamus produced an additional facilitation dynamic in cortex not observed with sensory stimulation. Thalamic neurons showed enhanced bursting activity in response to artificial stimulation, suggesting that bursting dynamics may underlie the facilitation mechanism we observed in cortex. To test this experimentally, we directly depolarized the thalamus, using optogenetic modulation of the firing activity to shift from a burst to a tonic mode. In the optogenetically depolarized thalamic state, the cortical facilitation dynamic was completely abolished. Together, the results obtained here from simple probes suggest that thalamic state, and ultimately thalamic bursting, may play a key role in shaping more complex stimulus-evoked dynamics in the thalamocortical pathway., New & Noteworthy: For the first time, we have been able to utilize optogenetic modulation of thalamic firing modes combined with optical imaging of cortex in the rat vibrissa system to directly test the role of thalamic state in shaping cortical response properties., (Copyright © 2017 the American Physiological Society.)