Neuroscience

ALS is characterized by progressive inability to execute movements. Motor neurons innervating fast-twitch muscle-fibers preferentially degenerate. The reason for this differential vulnerability and its consequences on motor output is not known. Here, we uncover that fast motor neurons receive stronger inhibitory synaptic inputs than slow motor neurons, and disease progression in the SOD1G93A mouse model leads to specific loss of inhibitory synapses onto fast motor neurons. Inhibitory V1 interneurons show similar innervation pattern and loss of synapses.

Neurotransmitter release is a highly controlled process by which synapses can critically regulate information transfer within neural circuits. While presynaptic receptors - typically activated by neurotransmitters and modulated by neuromodulators - provide a powerful way of fine-tuning synaptic function, their contribution to activity-dependent changes in transmitter release remains poorly understood.

This protocol describes the preparation of the mouse organ of Corti for RNAscope, immunolabeling, confocal microscopy, and quantitative image analysis to examine transcript and protein localization, sensory hair cells, and synapses. This protocol can be applied to mice and other rodents (juvenile and adult) and can be adapted for other techniques, including electrophysiology and RNA sequencing. This protocol features minimal tissue processing to preserve viability for downstream assays, while isolating the organ of Corti is the most challenging step.

The jugular-nodose ganglia contain the sensory peripheral neurons of the vagus nerve, linking visceral organs to the medulla oblongata. Accessing these ganglia in smaller animals without damaging the vascular and neural structures may be challenging, as ganglionic fibers imbed deeply into the carotid sheath, and vagal parasympathetic fibers cross through the interior of the ganglia. We describe a practical protocol for locating and accessing the mouse jugular-nodose ganglia _in vivo_, including instructions for intraganglionic injections and postperfusion dissection.

Epidemiological studies have shown that environmental insults and maternal stress during pregnancy increase the risk of several psychiatric disorders in the offspring. Converging lines of evidence from humans, as well as from rodent models, suggest that prenatal stress (PNS) interferes with fetal development, ultimately determining changes in brain maturation and function that may lead to the onset of neuropsychiatric disorders.

Responding to different dynamic levels of stress is critical for mammalian survival. Disruption of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) signaling is proposed to underlie hypothalamic-pituitary-adrenal (HPA) axis dysregulation observed in stress-related psychiatric disorders. In this study, we show that FK506-binding protein 51 (FKBP5) plays a critical role in fine-tuning MR:GR balance in the hippocampus.

Sensorimotor gating is a fundamental pre-attentive process that is defined as the inhibition of a motor response by a sensory event. Sensorimotor gating, commonly measured using the prepulse inhibition (PPI) of the auditory startle reflex task, is impaired in patients suffering from various neurological and psychiatric disorders. PPI deficits are a hallmark of schizophrenia, and they are often associated with attention and other cognitive impairments.

Regulation of Kiss1 transcription is crucial to the development and function of the reproductive axis. The homeodomain transcription factor, ventral anterior homeobox 1 (VAX1), has been implicated as a potential regulator of Kiss1 transcription. However, it is unknown whether VAX1 directly mediates transcription within kisspeptin neurons or works indirectly by acting upstream of kisspeptin neuron populations. This study tested the hypothesis that VAX1 within kisspeptin neurons regulates Kiss1 gene expression.

In sensory systems of the brain, mechanisms exist to extract distinct features from stimuli to generate a variety of behavioural repertoires. These often correspond to different cell types at various stages in sensory processing. In the mammalian olfactory system, complex information processing starts in the olfactory bulb, whose output is conveyed by mitral and tufted cells (MCs and TCs). Despite many differences between them, and despite the crucial position they occupy in the information hierarchy, Cre-driver lines that distinguish them do not yet exist.

APOE and Trem2 are major genetic risk factors for Alzheimer's disease (AD), but how they affect microglia response to Aβ remains unclear. Here we report an APOE isoform-specific phospholipid signature with correlation between human APOEε3/3 and APOEε4/4 AD brain and lipoproteins from astrocyte conditioned media of APOE3 and APOE4 mice. Using preclinical AD mouse models, we show that APOE3 lipoproteins, unlike APOE4, induce faster microglial migration towards injected Aβ, facilitate Aβ uptake, and ameliorate Aβ effects on cognition.