Temporal scaling of motor cortical dynamics reveals hierarchical control of vocal production.

Neocortical activity is thought to mediate voluntary control over vocal production, but the underlying neural mechanisms remain unclear. In a highly vocal rodent, the male Alston's singing mouse, we investigate neural dynamics in the orofacial motor cortex (OMC), a structure critical for vocal behavior. We first describe neural activity that is modulated by component notes (~100 ms), probably representing sensory feedback. At longer timescales, however, OMC neurons exhibit diverse and often persistent premotor firing patterns that stretch or compress with song duration (~10 s). Using computational modeling, we demonstrate that such temporal scaling, acting through downstream motor production circuits, can enable vocal flexibility. These results provide a framework for studying hierarchical control circuits, a common design principle across many natural and artificial systems.

Neural dynamics in the rodent motor cortex enables flexible control of vocal timing.

Neocortical activity is thought to mediate voluntary control over vocal production, but the underlying neural mechanisms remain unclear. In a highly vocal rodent, the Alston's singing mouse, we investigate neural dynamics in the orofacial motor cortex (OMC), a structure critical for vocal behavior. We first describe neural activity that is modulated by component notes (approx. 100 ms), likely representing sensory feedback. At longer timescales, however, OMC neurons exhibit diverse and often persistent premotor firing patterns that stretch or compress with song duration (approx. 10 s). Using computational modeling, we demonstrate that such temporal scaling, acting via downstream motor production circuits, can enable vocal flexibility. These results provide a framework for studying hierarchical control circuits, a common design principle across many natural and artificial systems.

Convergent behavioral strategies and neural computations during vocal turn-taking across diverse species.

Vocal exchanges between individuals are often coordinated in a temporally precise manner: one party is vocalizing while the other one is listening until the performance roles are switched. This vocal turn-taking behavior is widespread across the animal kingdom and thus provides an opportunity to study the neural circuit mechanisms from a comparative perspective. Although the physical prerequisites of the vocal tracts across animals can be different, the behavioral outcome of turn-taking is often similar with respect to vocal response timing and context-dependent adaptation. Here we review behavioral strategies of vocal turn-taking in diverse animals. Further, we highlight recent advances in studying the neural circuit mechanisms underlying vocal production and perception.

Long-range functional loops in the mouse olfactory system and their roles in computing odor identity.

Elucidating the neural circuits supporting odor identification remains an open challenge. Here, we analyze the contribution of the two output cell types of the mouse olfactory bulb (mitral and tufted cells) to decode odor identity and concentration and its dependence on top-down feedback from their respective major cortical targets: piriform cortex versus anterior olfactory nucleus. We find that tufted cells substantially outperform mitral cells in decoding both odor identity and intensity. Cortical feedback selectively regulates the activity of its dominant bulb projection cell type and implements different computations. Piriform feedback specifically restructures mitral responses, whereas feedback from the anterior olfactory nucleus preferentially controls the gain of tufted representations without altering their odor tuning. Our results identify distinct functional loops involving the mitral and tufted cells and their cortical targets. We suggest that in addition to the canonical mitral-to-piriform pathway, tufted cells and their target regions are ideally positioned to compute odor identity.

Using focal cooling to link neural dynamics and behavior.

Establishing a causal link between neural function and behavioral output has remained a challenging problem. Commonly used perturbation techniques enable unprecedented control over intrinsic activity patterns and can effectively identify crucial circuit elements important for specific behaviors. However, these approaches may severely disrupt activity, precluding an investigation into the behavioral relevance of moment-to-moment neural dynamics within a specified brain region. Here we discuss the application of mild focal cooling to slow down intrinsic neural circuit activity while preserving its overall structure. Using network modeling and examples from multiple species, we highlight the power and versatility of focal cooling for understanding how neural dynamics control behavior and argue for its wider adoption within the systems neuroscience community.

Singing mice.

A Quick guide to singing mice.

Motor cortical control of vocal interaction in neotropical singing mice.

Like many adaptive behaviors, acoustic communication often requires rapid modification of motor output in response to sensory cues. However, little is known about the sensorimotor transformations that underlie such complex natural behaviors. In this study, we examine vocal exchanges in Alston's singing mouse (Scotinomys teguina). We find that males modify singing behavior during social interactions on a subsecond time course that resembles both traditional sensorimotor tasks and conversational speech. We identify an orofacial motor cortical region and, via a series of perturbation experiments, demonstrate a hierarchical control of vocal production, with the motor cortex influencing the pacing of singing behavior on a moment-by-moment basis, enabling precise vocal interactions. These results suggest a systems-level framework for understanding the sensorimotor transformations that underlie natural social interactions.

Ready, Steady, Go! Imaging Cortical Activity during Movement Planning and Execution.

In this issue of Neuron, Chen et al. (2017) examine premotor activity representing motor planning, Allen et al. (2017) observe the global representation of goal-directed movement on the cortical network, and Makino et al. (2017) track changes in such dynamics throughout learning.

An Interglomerular Circuit Gates Glomerular Output and Implements Gain Control in the Mouse Olfactory Bulb.

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.

Label-free dopamine imaging in live rat brain slices.

Dopaminergic neurotransmission has been investigated extensively, yet direct optical probing of dopamine has not been possible in live cells. Here we image intracellular dopamine with sub-micrometer three-dimensional resolution by harnessing its intrinsic mid-ultraviolet (UV) autofluorescence. Two-photon excitation with visible light (540 nm) in conjunction with a non-epifluorescent detection scheme is used to circumvent the UV toxicity and the UV transmission problems. The method is established by imaging dopamine in a dopaminergic cell line and in control cells (glia), and is validated by mass spectrometry. We further show that individual dopamine vesicles/vesicular clusters can be imaged in cultured rat brain slices, thereby providing a direct visualization of the intracellular events preceding dopamine release induced by depolarization or amphetamine exposure. Our technique opens up a previously inaccessible mid-ultraviolet spectral regime (excitation ~270 nm, emission < 320 nm) for label-free imaging of native molecules in live tissue.