Neuroscience

Single-cell genomics identifies cell type-specific molecular changes in autism.

Despite the clinical and genetic heterogeneity of autism, bulk gene expression studies show that changes in the neocortex of autism patients converge on common genes and pathways. However, direct assessment of specific cell types in the brain affected by autism has not been feasible until recently. We used single-nucleus RNA sequencing of cortical tissue from patients with autism to identify autism-associated transcriptomic changes in specific cell types.

Synergistic Nigral Output Pathways Shape Movement.

Locomotion relies on the activity of basal ganglia networks, where, as the output, the substantia nigra pars reticulata (SNr) integrates incoming signals and relays them to downstream areas. The cellular and circuit substrates of such a complex function remain unclear.

How Gastrin-Releasing Peptide Opens the Spinal Gate for Itch.

Spinal transmission of pruritoceptive (itch) signals requires transneuronal signaling by gastrin-releasing peptide (GRP) produced by a subpopulation of dorsal horn excitatory interneurons. These neurons also express the glutamatergic marker vGluT2, raising the question of why glutamate alone is insufficient for spinal itch relay.

Striatal Low-Threshold Spiking Interneurons Regulate Goal-Directed Learning.

The dorsomedial striatum (DMS) is critically involved in motor control and reward processing, but the specific neural circuit mediators are poorly understood. Recent evidence highlights the extensive connectivity of low-threshold spiking interneurons (LTSIs) within local striatal circuitry; however, the in vivo function of LTSIs remains largely unexplored.

Parvalbumin Interneurons Determine Emotional Valence Through Modulating Accumbal Output Pathways

Parvalbumin (PV) expressing GABAergic interneurons provide large source of GABA to spiny projection neurons (SPNs) in the striatum. However, the roles of PV+ interneurons in the regulation of SPNs in the ventral striatum and emotional states are largely unknown. Here, we investigated whether stimulation of ventral striatal (accumbal) PV+ interneurons would drive emotional valence in mice. We found that during conditioned place preference (CPP) training, activation of accumbal PV+ interneurons evoked place preference while suppressing them resulted in conditioned place aversion (CPA).

Pou4f1 defines a subgroup of Type I spiral ganglion neurons and is necessary for normal inner hair cell presynaptic Ca2+ signaling.

Acoustic signals are relayed from the ear to the brain via spiral ganglion neurons (SGNs) that receive auditory information from the cochlear inner hair cells and transmit that information to the cochlear nucleus of the brainstem.

Tridimensional mapping of Phox2b expressing neurons in the brainstem of adult Macaca fascicularis and identification of the retrotrapezoid nucleus.

From a whole macaque (m. fascicularis) brain, serial transversal sections of the brainstem were made using a blockface setup that takes high-definition pictures of the organ surface, before microtome slicing.

Loss of Shh signaling in the neocortex reveals heterogeneous cell recovery responses from distinct oligodendrocyte populations.

The majority of oligodendrocytes in the neocortex originate from neural progenitors that reside in the dorsal forebrain. We recently showed that Sonic Hedgehog (Shh) signaling in these dorsal progenitors is required to produce normal numbers of neocortical oligodendrocytes during embryonic development. Conditional deletion of the Shh signaling effector, Smo, in dorsal progenitors caused a dramatic reduction in oligodendrocyte numbers in the embryonic neocortex.

Disordered breathing in a mouse model of Dravet syndrome.

Dravet syndrome (DS) is a form of epilepsy with a high incidence of sudden unexpected death in epilepsy (SUDEP). Respiratory failure is a leading cause of SUDEP, and DS patients' frequently exhibit disordered breathing. Despite this, mechanisms underlying respiratory dysfunction in DS are unknown.

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