Olfactory cortical neurons read out a relative time code in the olfactory bulb

Odor stimulation evokes complex spatiotemporal activity in the olfactory bulb, suggesting that the identity of activated neurons as well as the timing of their activity convey information about odors. However, whether and how downstream neurons decipher these temporal patterns remains debated. We addressed this question by measuring the spiking activity of downstream neurons while optogenetically stimulating two foci in the olfactory bulb with varying relative timing in mice. We found that the overall spike rates of piriform cortex neurons were sensitive to the relative timing of activation. Posterior piriform cortex neurons showed higher sensitivity to relative input times than neurons in the anterior piriform cortex. In contrast, olfactory bulb neurons rarely showed such sensitivity. Thus, the brain can transform a relative time code in the periphery into a firing-rate-based representation in central brain areas, providing evidence for the relevance of relative time-based code in the olfactory bulb

A gut-to-brain signal of fluid osmolarity controls thirst satiation.

Satiation is the process by which eating and drinking reduce appetite. For thirst, oropharyngeal cues have a critical role in driving satiation by reporting to the brain the volume of fluid that has been ingested1-12. By contrast, the mechanisms that relay the osmolarity of ingested fluids remain poorly understood. Here we show that the water and salt content of the gastrointestinal tract are precisely measured and then rapidly communicated to the brain to control drinking behaviour in mice. We demonstrate that this osmosensory signal is necessary and sufficient for satiation during normal drinking, involves the vagus nerve and is transmitted to key forebrain neurons that control thirst and vasopressin secretion. Using microendoscopic imaging, we show that individual neurons compute homeostatic need by integrating this gastrointestinal osmosensory information with oropharyngeal and blood-borne signals. These findings reveal how the fluid homeostasis system monitors the osmolarity of ingested fluids to dynamically control drinking behaviour

Connectional architecture of a mouse hypothalamic circuit node controlling social behavior

Type 1 estrogen receptor-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl^(Esr1)) play a causal role in the control of social behaviors, including aggression. Here we use six different viral-genetic tracing methods to systematically map the connectional architecture of VMHvl^(Esr1) neurons. These data reveal a high level of input convergence and output divergence (“fan-in/fan-out”) from and to over 30 distinct brain regions, with a high degree (∼90%) of bidirectionality, including both direct as well as indirect feedback. Unbiased collateralization mapping experiments indicate that VMHvl^(Esr1) neurons project to multiple targets. However, we identify two anatomically distinct subpopulations with anterior vs. posterior biases in their collateralization targets. Nevertheless, these two subpopulations receive indistinguishable inputs. These studies suggest an overall system architecture in which an anatomically feed-forward sensory-to-motor processing stream is integrated with a dense, highly recurrent central processing circuit. This architecture differs from the “brain-inspired,” hierarchical feed-forward circuits used in certain types of artificial intelligence networks

Scalable control of mounting and attack by Esr1^+ neurons in the ventromedial hypothalamus

Social behaviours, such as aggression or mating, proceed through a series of appetitive and consummatory phases that are associated with increasing levels of arousal. How such escalation is encoded in the brain, and linked to behavioural action selection, remains an unsolved problem in neuroscience. The ventrolateral subdivision of the murine ventromedial hypothalamus (VMHvl) contains neurons whose activity increases during male–male and male–female social encounters. Non-cell-type-specific optogenetic activation of this region elicited attack behaviour, but not mounting. We have identified a subset of VMHvl neurons marked by the oestrogen receptor 1 (Esr1), and investigated their role in male social behaviour. Optogenetic manipulations indicated that Esr1^+ (but not Esr1^−) neurons are sufficient to initiate attack, and that their activity is continuously required during ongoing agonistic behaviour. Surprisingly, weaker optogenetic activation of these neurons promoted mounting behaviour, rather than attack, towards both males and females, as well as sniffing and close investigation. Increasing photostimulation intensity could promote a transition from close investigation and mounting to attack, within a single social encounter. Importantly, time-resolved optogenetic inhibition experiments revealed requirements for Esr1^+ neurons in both the appetitive (investigative) and the consummatory phases of social interactions. Combined optogenetic activation and calcium imaging experiments in vitro, as well as c-Fos analysis in vivo, indicated that increasing photostimulation intensity increases both the number of active neurons and the average level of activity per neuron. These data suggest that Esr1^+ neurons in VMHvl control the progression of a social encounter from its appetitive through its consummatory phases, in a scalable manner that reflects the number or type of active neurons in the population

Visual Tuning Properties of Genetically Identified Layer 2/3 Neuronal Types in the Primary Visual Cortex of Cre-Transgenic Mice

The putative excitatory and inhibitory cell classes within the mouse primary visual cortex V1 have different functional properties as studied using recording microelectrode. Excitatory neurons show high selectivity for the orientation angle of moving gratings while the putative inhibitory neurons show poor selectivity. However, the study of selectivity of the genetically identified interneurons and their subtypes remain controversial. Here we use novel Cre-driver and reporter mice to identify genetic subpopulations in vivo for two-photon calcium dye imaging: Wfs1(+)/Gad1(−) mice that labels layer 2/3 excitatory cell population and Pvalb(+)/Gad1(+) mice that labels a genetic subpopulation of inhibitory neurons. The cells in both mice were identically labeled with a tdTomato protein, visible in vivo, using a Cre-reporter line. We found that the Wfs1(+) cells exhibited visual tuning properties comparable to the excitatory population, i.e., high selectivity and tuning to the angle, direction, and spatial frequency of oriented moving gratings. The functional tuning of Pvalb(+) neurons was consistent with previously reported narrow-spiking interneurons in microelectrode studies, exhibiting poorer selectivity than the excitatory neurons. This study demonstrates the utility of Cre-transgenic mouse technology in selective targeting of subpopulations of neurons and makes them amenable to structural, functional, and connectivity studies

SmartScope2: Simultaneous Imaging and Reconstruction of Neuronal Morphology.

Quantitative analysis of neuronal morphology is critical in cell type classification and for deciphering how structure gives rise to function in the brain. Most current approaches to imaging and tracing neuronal 3D morphology are data intensive. We introduce SmartScope2, the first open source, automated neuron reconstruction machine integrating online image analysis with automated multiphoton imaging. SmartScope2 takes advantage of a neuron\u27s sparse morphology to improve imaging speed and reduce image data stored, transferred and analyzed. We show that SmartScope2 is able to produce the complex 3D morphology of human and mouse cortical neurons with six-fold reduction in image data requirements and three times the imaging speed compared to conventional methods