Summary Complex animal behaviors are likely built from simpler modules, but their systematic identification in mammals remains a significant challenge. Here we use depth imaging to show that three-dimensional (3D) mouse pose dynamics are structured at the sub-second timescale. Computational modeling of these fast dynamics effectively describes mouse behavior as a series of reused and stereotyped modules with defined transition probabilities. We demonstrate this combined 3D imaging and machine learning method can be used to unmask potential strategies employed by the brain to adapt to the environment, to capture both predicted and previously-hidden phenotypes caused by genetic or neural manipulations, and to systematically expose the global structure of behavior within an experiment. This work reveals that mouse body language is built from identifiable components and is organized in a predictable fashion; deciphering this language establishes an objective framework for characterizing the influence of environmental cues, genes and neural activity on behavior.

SummaryMultimodal objects and events activate many sensory cortical areas simultaneously. This is possibly reflected in reciprocal modulations of neuronal activity, even at the level of primary cortical areas. However, the synaptic character of these interareal interactions, and their impact on synaptic and behavioral sensory responses are unclear. Here, we found that activation of auditory cortex by a noise burst drove local GABAergic inhibition on supragranular pyramids of the mouse primary visual cortex, via cortico-cortical connections. This inhibition was generated by sound-driven excitation of a limited number of cells in infragranular visual cortical neurons. Consequently, visually driven synaptic and spike responses were reduced upon bimodal stimulation. Also, acoustic stimulation suppressed conditioned behavioral responses to a dim flash, an effect that was prevented by acute blockade of GABAergic transmission in visual cortex. Thus, auditory cortex activation by salient stimuli degrades potentially distracting sensory processing in visual cortex by recruiting local, translaminar, inhibitory circuits.

Postsynaptic long-term potentiation of inhibition (iLTP) can rely on increased GABAA receptors (GABAARs) at synapses by promoted exocytosis. However, the molecular mechanisms that enhance the clustering of postsynaptic GABAARs during iLTP remain obscure. Here we demonstrate that during chemically induced iLTP (chem-iLTP), GABAARs are immobilized and confined at synapses, as revealed by single-particle tracking of individual GABAARs in cultured hippocampal neurons. Chem-iLTP expression requires synaptic recruitment of the scaffold protein gephyrin from extrasynaptic areas, which in turn is promoted by CaMKII-dependent phosphorylation of GABAAR-β3-Ser383. Impairment of gephyrin assembly prevents chem-iLTP and, in parallel, blocks the accumulation and immobilization of GABAARs at synapses. Importantly, an increase of gephyrin and GABAAR similar to those observed during chem-iLTP in cultures were found in the rat visual cortex following an experience-dependent plasticity protocol that potentiates inhibitory transmission in vivo. Thus, phospho-GABAAR-β3-dependent accumulation of gephyrin at synapses and receptor immobilization are crucial for iLTP expression and are likely to modulate network excitability.

Multisensory integration (MI) is crucial for sensory processing, but it is unclear how MI is organized in cortical microcircuits. Whole-cell recordings in a mouse visuotactile area located between primary visual and somatosensory cortices revealed that spike responses were less bimodal than synaptic responses but displayed larger multisensory enhancement. MI was layer and cell type specific, with multisensory enhancement being rare in the major class of inhibitory interneurons and in the output infragranular layers. Optogenetic manipulation of parvalbumin-positive interneuron activity revealed that the scarce MI of interneurons enables MI in neighboring pyramids. Finally, single-cell resolution calcium imaging revealed a gradual merging of modalities: unisensory neurons had higher densities toward the borders of the primary cortices, but were located in unimodal clusters in the middle of the cortical area. These findings reveal the role of different neuronal subcircuits in the synaptic process of MI in the rodent parietal cortex.

The cortex organizes sensory information to enable discrimination and generalization 1 – 4 . Systematic representations of chemical odor space have not been described in olfactory cortex, and so it remains unclear how odor relationships are encoded to place chemically distinct but similar odors, like lemon and orange, into perceptual categories, like citrus 5 – 7 . Here we demonstrate that both the piriform cortex (PCx) and its sensory inputs from the olfactory bulb represent chemical odor relationships through correlated patterns of activity. However, cortical odor codes differ from those in the bulb: cortex more strongly clusters together representations for related odors, selectively rewrites pairwise odor relationships, and better matches odor perception. The bulb-to-cortex transformation depends upon the associative network originating within PCx, and can be reshaped by passive odor experience. Thus, cortex actively builds a structured representation of chemical odor space that highlights odor relationships; this representation is similar across individuals but remains plastic, suggesting a means through which the olfactory system can assign related odor cues to common and yet personalized percepts.