The ventral visual stream of the human brain is subdivided into patches with categorical stimulus preferences, like faces or scenes. However, the functional organization within these areas is less clear. Here, we used functional magnetic resonance imaging and vertex-wise tuning models to independently probe spatial and face-part preferences in the inferior occipital gyrus (IOG) of healthy adult males and females. The majority of responses were well explained by Gaussian population tuning curves for both retinotopic location and the preferred relative position within a face. Parameter maps revealed a common gradient of spatial and face-part selectivity, with the width of tuning curves drastically increasing from posterior to anterior IOG. Tuning peaks clustered more idiosyncratically but were also correlated across maps of visual and face space. Preferences for the upper visual field went along with significantly increased coverage of the upper half of the face, matching recently discovered biases in human ...

Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder caused by a trinucleotide expansion in exon 1 of the huntingtin ( HTT ) gene. Cell death in HD occurs primarily in striatal medium spiny neurons (MSNs), but the involvement of specific MSN subtypes and of other striatal cell types remains poorly understood. To gain insight into cell type-specific disease processes, we studied the nuclear transcriptomes of 4524 cells from the striatum of a genetically precise knock-in mouse model of the HD mutation, Htt Q175 /+, and from wild-type controls. We used 14- to 15-month-old male mice, a time point at which multiple behavioral, neuroanatomical, and neurophysiological changes are present but at which there is no known cell death. Thousands of differentially expressed genes (DEGs) were distributed across most striatal cell types, including transcriptional changes in glial populations that are not apparent from RNA-seq of bulk tissue. Reconstruction of cell type-specific transcriptional n...

The brainstem dorsal periaqueductal gray (dPAG) has been widely recognized as being a vital node orchestrating the responses to innate threats. Intriguingly, recent evidence also shows that the dPAG mediates defensive responses to fear conditioned contexts. However, it is unknown whether the dPAG displays independent or shared patterns of activation during exposure to innate and conditioned threats. It is also unclear how dPAG ensembles encode and predict diverse defensive behaviors. To address this question, we used miniaturized microscopes to obtain recordings of the same dPAG ensembles during exposure to a live predator and a fear conditioned context in male mice. dPAG ensembles encoded not only distance to threat, but also relevant features, such as predator speed and angular offset between mouse and threat. Furthermore, dPAG cells accurately encoded numerous defensive behaviors, including freezing, stretch-attend postures, and escape. Encoding of behaviors and of distance to threat occurred independen...

The initiation and propagation of the action potential (AP) along an axon allows neurons to convey information rapidly and across distant sites. Although AP properties have typically been characterized at the soma and proximal axon, knowledge of the propagation of APs toward distal axonal domains of mammalian CNS neurons remains limited. We used genetically encoded voltage indicators (GEVIs) to image APs with submillisecond temporal resolution simultaneously at different locations along the long axons of dissociated hippocampal neurons from rat embryos of either sex. We found that APs became sharper and showed remarkable fidelity as they traveled toward distal axons, even during a high-frequency train. Blocking voltage-gated potassium channels (Kv) with 4-AP resulted in an increase in AP width in all compartments, which was stronger at distal locations and exacerbated during AP trains. We conclude that the higher levels of Kv channel activity in distal axons serve to sustain AP fidelity, conveying a reliab...

Neural activity is diverse, and varies depending on brain regions and sleep/wakefulness states. However, whether astrocyte activity differs between sleep/wakefulness states, and whether there are differences in astrocyte activity among brain regions remain poorly understood. Therefore, in this study, we recorded astrocyte intracellular calcium (Ca2+) concentrations of mice during sleep/wakefulness states in the cortex, hippocampus, hypothalamus, cerebellum, and pons using fiber photometry. For this purpose, male transgenic mice expressing the genetically encoded ratiometric Ca2+ sensor YCnano50 specifically in their astrocytes were used. We demonstrated that Ca2+ levels in astrocytes substantially decrease during rapid eye movement (REM) sleep, and increase after the onset of wakefulness. In contrast, differences in Ca2+ levels during non-REM (NREM) sleep were observed among the different brain regions, and no significant decrease was observed in the hypothalamus and pons. Further analyses focusing on the ...

Victoria Gonzalez Sabater, Mark Rigby, and Juan Burrone (see pages [5372–5385][1]) Synaptic potentials evoked in neuronal dendrites and soma summate and converge at the axon initial segment, where, if sufficient depolarization occurs, an action potential is generated. By sequentially activating

Rapid sensory adaptation is observed across all sensory systems, and strongly shapes sensory percepts in complex sensory environments. Yet despite its ubiquity and likely necessity for survival, the mechanistic basis is poorly understood. A wide range of primarily in vitro and anesthetized studies have demonstrated the emergence of adaptation at the level of primary sensory cortex, with only modest signatures in earlier stages of processing. The nature of rapid adaptation and how it shapes sensory representations during wakefulness, and thus the potential role in perceptual adaptation, is underexplored, as are the mechanisms that underlie this phenomenon. To address these knowledge gaps, we recorded spiking activity in primary somatosensory cortex (S1) and the upstream ventral posteromedial (VPm) thalamic nucleus in the vibrissa pathway of awake male and female mice, and quantified responses to whisker stimuli delivered in isolation and embedded in an adapting sensory background. We found that cortical sen...

Oligodendrocyte progenitor cells (OPCs) are specified from discrete precursor populations during gliogenesis and migrate extensively from their origins, ultimately distributing throughout the brain and spinal cord during early development. Subsequently, a subset of OPCs differentiates into mature oligodendrocytes, which myelinate axons. This process is necessary for efficient neuronal signaling and organism survival. Previous studies have identified several factors that influence OPC development, including excitatory glutamatergic synapses that form between neurons and OPCs during myelination. However, little is known about how glutamate signaling affects OPC migration before myelination. In this study, we use in vivo, time-lapse imaging in zebrafish in conjunction with genetic and pharmacological perturbation to investigate OPC migration and myelination when the GluR4A ionotropic glutamate receptor subunit is disrupted. In our studies, we observed that gria4a mutant embryos and larvae displayed abnormal O...

Sleep and sleep loss are thought to impact synaptic plasticity, and recent studies have shown that sleep and sleep deprivation (SD) differentially affect gene transcription and protein translation in the mammalian forebrain. However, much less is known regarding how sleep and SD affect these processes in different microcircuit elements within the hippocampus and neocortex, for example, in inhibitory versus excitatory neurons. Here, we use translating ribosome affinity purification (TRAP) and in situ hybridization to characterize the effects of sleep versus SD on abundance of ribosome-associated transcripts in Camk2a-expressing (Camk2a+) pyramidal neurons and parvalbumin-expressing (PV+) interneurons in the hippocampus and neocortex of male mice. We find that while both Camk2a+ neurons and PV+ interneurons in neocortex show concurrent SD-driven increases in ribosome-associated transcripts for activity-regulated effectors of plasticity and transcriptional regulation, these transcripts are minimally affected ...