Classical studies of mammalian movement control define a prominent role for the primary motor cortex. Investigating the mouse whisker system, we found an additional and equally direct pathway for cortical motor control driven by the primary somatosensory cortex. Whereas activity in primary motor cortex directly evokes exploratory whisker protraction, primary somatosensory cortex directly drives whisker retraction, providing a rapid negative feedback signal for sensorimotor integration. Motor control by sensory cortex suggests the need to reevaluate the functional organization of cortical maps.

Summary Odors elicit distributed activation of glomeruli in the olfactory bulb (OB). Crosstalk between co-active glomeruli has been proposed to perform a variety of computations, facilitating efficient extraction of sensory information by the cortex. Dopaminergic/GABAergic cells in the OB, which can be identified by their expression of the dopamine transporter (DAT), provide the earliest opportunity for such crosstalk. Here we show in mice that DAT+ cells carry concentration dependent odor signals and broadcast focal glomerular inputs throughout the OB to cause suppression of mitral/tufted (M/T) cell firing, an effect that is mediated by the external tufted (ET) cells coupled to DAT+ cells via chemical and electrical synapses. We find that DAT+ cells implement gain control and decorrelate odor representations in the M/T cell population. Our results further indicate that ET cells are gatekeepers of glomerular output and prime determinants of M/T responsiveness.

Psychophysical tasks for non-human primates have been instrumental in studying circuits underlying perceptual decision-making. To obtain greater experimental flexibility, these tasks have subsequently been adapted for use in freely moving rodents. However, advances in functional imaging and genetic targeting of neuronal populations have made it critical to develop similar tasks for head-fixed mice. Although head-fixed mice have been trained in two-alternative forced choice tasks before, these tasks were not self-initiated, making it difficult to attribute error trials to perceptual or decision errors as opposed to mere lapses in task engagement. Here, we describe a paradigm for head-fixed mice with three lick spouts, analogous to the well-established 3-port paradigm for freely moving rodents. Mice readily learned to initiate trials on the center spout and performed around 200 self-initiated trials per session, reaching good psychometric performance within two weeks of training. We expect this paradigm will be useful to study the role of defined neural populations in sensory processing and decision-making.

Animals' choice behavior is characterized by two main tendencies: taking actions that led to rewards and repeating past actions. Theory suggests these strategies may be reinforced by different types of dopaminergic teaching signals: reward prediction error (RPE) to reinforce value-based associations and movement-based action prediction errors to reinforce value-free repetitive associations. Here we use an auditory-discrimination task in mice to show that movement-related dopamine activity in the tail of the striatum encodes the hypothesized action prediction error signal. Causal manipulations reveal that this prediction error serves as a value-free teaching signal that supports learning by reinforcing repeated associations. Computational modeling and experiments demonstrate that action prediction errors cannot support reward-guided learning but when paired with the RPE circuity they serve to consolidate stable sound-action associations in a value-free manner. Together we show that there are two types of dopaminergic prediction errors that work in tandem to support learning.

The activity of neurons in the auditory cortex is driven by both sounds and non-sensory context. To investigate the neuronal correlates of non-sensory context, we trained head-fixed mice to perform a two-alternative choice auditory task in which either reward or stimulus expectation (prior) was manipulated in blocks. Using two-photon calcium imaging to record populations of single neurons in auditory cortex, we found that both sensory and reward expectation modulated the activity of these neurons. Interestingly, the optimal decoder was stable even in the face of variable sensory representations. Neither the context nor the mouse's choice could be reliably decoded from the recorded auditory activity. Our findings suggest that in spite of modulation of auditory cortical activity by task priors, auditory cortex does not represent sufficient information about these priors to exploit them optimally and that decisions in this task require that rapidly changing sensory information be combined with more slowly varying task information extracted and represented in brain regions other than auditory cortex.