Summary Adaptation is fundamental to life. All organisms adapt over timescales that span from evolution to generations and lifetimes to moment-by-moment interactions. The nervous system is particularly adept at rapidly adapting to change, and this in fact may be one of its fundamental principles of organization and function. Rapid forms of sensory adaptation have been well-documented across all sensory modalities in a wide range of organisms, yet we do not have a comprehensive understanding of the adaptive cellular mechanisms that ultimately give rise to the corresponding percepts due in part to the complexity of the circuitry. In this Perspective, we aim to build links between adaptation at multiple scales of neural circuitry by investigating the differential adaptation across brain regions and sub-regions and across specific cell-types, for which the explosion of modern tools has just begun to enable. This investigation points to a set of challenges for the field to link functional observations to adaptive properties of the neural circuit that ultimately underlie percepts.

Optogenetic techniques enable precise excitation and inhibition of firing in specified neuronal populations and artifact-free recording of firing activity. Several studies have suggested that optical stimulation provides the precision and dynamic range requisite for closed-loop neuronal control, but no approach yet permits feedback control of neuronal firing. Here we present the ‘optoclamp’, a feedback control technology that provides continuous, real-time adjustments of bidirectional optical stimulation in order to lock spiking activity at specified targets over timescales ranging from seconds to days. We demonstrate how this system can be used to decouple neuronal firing levels from ongoing changes in network excitability due to multi-hour periods of glutamatergic or GABAergic neurotransmission blockade in vitro as well as impinging vibrissal sensory drive in vivo. This technology enables continuous, precise optical control of firing in neuronal populations in order to disentangle causally related variables of circuit activation in a physiologically and ethologically relevant manner.DOI: http://dx.doi.org/10.7554/eLife.07192.001

Summary It has been posited that the regulation of burst/tonic firing in the thalamus could function as a mechanism for controlling not only how much, but what kind of information is conveyed to downstream cortical targets. Yet how this gating mechanism is adaptively modulated on fast time scales by ongoing sensory inputs in rich sensory environments remains unknown. Using single unit recordings in the rat vibrissa thalamus (VPm), we found that the degree of bottom-up adaptation modulated thalamic burst/tonic firing as well as the synchronization of bursting across the thalamic population along a continuum for which the extremes facilitate detection or discrimination of sensory inputs. Optogenetic control of baseline membrane potential in thalamus further suggests that this regulation may result from an interplay between adaptive changes in thalamic membrane potential and synaptic drive from inputs to thalamus, setting the stage for an intricate control strategy upon which cortical computation is built.