Differential Excitation of Distally versus Proximally Targeting Cortical Interneurons by Unitary Thalamocortical Bursts.

UNLABELLED

Thalamocortical neurons relay sensory and motor information to the neocortex using both single spikes and bursts; bursts prevail during low-vigilance states but also occur during awake behavior. Bursts are suggested to provide an alerting signal to the cortex and enhance stimulus detection, but the synaptic mechanisms underlying these effects are not clear, because the postsynaptic responses of different subtypes of cortical neurons to unitary thalamocortical bursts are mostly unknown. Using optogenetically guided recordings in mouse thalamocortical slices, we achieved the first reported paired intracellular recordings from nine monosynaptically connected thalamic and cortical neurons, including principal cells and two subtypes of inhibitory interneurons, and compared between cortical responses to single thalamocortical spikes and bursts. In 18 additional cortical neurons, we elicited unitary burst responses optogenetically. Short-term dynamics and temporal summation of burst-evoked EPSPs were cell-type dependent: in principal cells and somatostatin-containing (SOM), but not fast-spiking (FS), interneurons, peak response during a burst was on average more than twofold larger than the response to the first spike. Thus, firing a burst instead of a single spike would more than double the probability of firing in postsynaptic excitatory neurons and in SOM, but not FS, interneurons. Consistent with this prediction, FS interneurons held near firing threshold fired most often on the first burst component, whereas SOM interneurons fired only on the second or later components. By increasing excitation of principal cells together with SOM-mediated, distally directed inhibition, thalamocortical bursts could momentarily enhance the saliency of the ascending sensory stimulus over less urgent, top-down inputs.

SIGNIFICANCE STATEMENT

Thalamocortical neurons relay sensory and motor information to the cerebral cortex using both single spikes and high-frequency bursts, but the function of bursts is not fully understood. Using brain slices from mouse somatosensory thalamus and cortex, we achieved the first dual recordings of directly connected thalamic and cortical neurons and compared between cortical responses to single thalamic spikes and to bursts. We report that bursts enhanced the responses of excitatory neurons and of inhibitory interneurons that preferentially target dendrites. A potential consequence is that bursts will enhance the response to the immediate sensory event over responses to less urgent, modulatory inputs.