What happens in the brain when we feel touch? We feel the same tactile stimulus differently depending on surrounding contexts or one’s expectations, but why? Our goal is to understand the neuronal mechanisms by which the cortex processes tactile information to generate percepts of stimuli or make behavioral decisions. We are particularly interested in computational principles implemented at the levels from synapses to local circuits. An integrated approach is essential to dissect complex neuronal activity in behaving animals. We, therefore, combine various experimental techniques, including two-photon calcium imaging, electrophysiology, and optogenetics, with behavioral experiments in mice. To study tactile sensation, we use the mouse whisker system as an experimental model.
The somatosensory cortex (S1) receives tactile sensory input from different body parts via the thalamus. S1 activity does not solely rely on external inputs. Indeed, S1 also receives a variety of inputs from other brain areas, such as cortical feedback and neuromodulatory (e.g., cholinergic and adrenergic) inputs. These inputs are thought to orchestrate internal states within S1 and dynamically modulate the processing of incoming tactile input. As yet, little is known about how the feedback and neuromodulatory inputs are organized in space and time within S1. By utilizing optical imaging, we investigate the spatiotemporal dynamics of the individual inputs at the local circuit and single-neuron levels. We will then intervene in the revealed dynamics to test their roles in animal’s perceptual performance and decision-making. We hope to understand the internal cortical dynamics, which may explain why the same stimulus is perceived differently across contexts.
How are external tactile inputs integrated with internal cortical activity (feedback and neuromodulatory inputs)? We try to identify the mechanistic substrates that mediate the integration at the cellular and circuit levels. At the cellular level, we have recently shown that calcium channel-mediated dendritic regenerative potentials (dendritic calcium spikes) in deep layer 5 pyramidal neurons play a critical role in tactile detection – regulating the perceptual threshold for detecting weak tactile stimulation (Takahashi et al., 2016; Takahashi et al., 2020). Our working hypothesis is that feedback and neuromodulatory inputs modulate the output gain of S1 during tactile detection by regulating active dendritic mechanisms. We will further extend this model to local inhibitory circuits that interconnect with pyramidal neurons to gain better insights into the integrative operation of S1 circuits in tactile processing.