Promotes Cognitive Function through Regulation of Cortical Sensorimotor Dynamics.

Perception, a cognitive construct, emerges through sensorimotor integration (SMI). The genetic mechanisms that shape SMI required for perception are unknown. Here, we demonstrate in mice that expression of the autism/intellectual disability gene, , in cortical excitatory neurons is required for formation of somatomotor networks that promote SMI-mediated perception.

Long-Lived Organotypic Slice Culture Model of the Rat Basolateral Amygdala.

Organotypic slice cultures (OTCs) have been employed in the laboratory since the early 1980s and have proved to be useful for the study of a number of neural systems. Our recent work focuses on the development of behavioral stress resilience induced by repeated daily injections of neuropeptide Y into the basolateral amygdala (BLA). Resilience develops over weeks, persisting to 8 weeks.

regulates experience-dependent cortical ensemble plasticity by promoting in vivo excitatory synapse strengthening.

A significant proportion of autism risk genes regulate synapse function, including plasticity, which is believed to contribute to behavioral abnormalities. However, it remains unclear how impaired synapse plasticity contributes to network-level processes linked to adaptive behaviors, such as experience-dependent ensemble plasticity. We found that , a major autism risk gene, promoted measures of experience-dependent excitatory synapse strengthening in the mouse cortex, including spike-timing-dependent glutamatergic synaptic potentiation and presynaptic bouton formation.

Contribution of NPY Y Receptors to the Reversible Structural Remodeling of Basolateral Amygdala Dendrites in Male Rats Associated with NPY-Mediated Stress Resilience.

Endogenous neuropeptide Y (NPY) and corticotrophin-releasing factor (CRF) modulate the responses of the basolateral amygdala (BLA) to stress and are associated with the development of stress resilience and vulnerability, respectively. We characterized persistent effects of repeated NPY and CRF treatment on the structure and function of BLA principal neurons in a novel organotypic slice culture (OTC) model of male rat BLA, and examined the contributions of specific NPY receptor subtypes to these neural and behavioral effects. In BLA principal neurons within the OTCs, repeated NPY treatment caused persistent attenuation of excitatory input and induced dendritic hypotrophy via Y receptor activation; conversely, CRF increased excitatory input and induced hypertrophy of BLA principal neurons.

NPY Receptors Reduce Tonic Action Potential-Independent GABA Currents in the Basolateral Amygdala.

Although NPY has potent anxiolytic actions within the BLA, selective activation of BLA NPY Y receptors (YRs) acutely increases anxiety by an unknown mechanism. Using male rat brain slice electrophysiology, we show that the selective YR agonist, [ahx]NPY, reduced the frequency of GABA-mediated mIPSCs in BLA principal neurons (PNs). [ahx]NPY also reduced tonic activation of GABA receptors (GABAR), which increased PN excitability through inhibition of a tonic, inwardly rectifying potassium current ( ).

SYNGAP1 heterozygosity disrupts sensory processing by reducing touch-related activity within somatosensory cortex circuits.

In addition to cognitive impairments, neurodevelopmental disorders often result in sensory processing deficits. However, the biological mechanisms that underlie impaired sensory processing associated with neurodevelopmental disorders are generally understudied and poorly understood. We found that SYNGAP1 haploinsufficiency in humans, which causes a sporadic neurodevelopmental disorder defined by cognitive impairment, autistic features, and epilepsy, also leads to deficits in tactile-related sensory processing.

NPY Induces Stress Resilience via Downregulation of in Principal Neurons of Rat Basolateral Amygdala.

Neuropeptide Y (NPY) expression is tightly linked with the development of stress resilience in rodents and humans. Local NPY injections targeting the basolateral amygdala (BLA) produce long-term behavioral stress resilience in male rats via an unknown mechanism. Previously, we showed that activation of NPY Y receptors hyperpolarizes BLA principal neurons (PNs) through inhibition of the hyperpolarization-activated, depolarizing H-current, The present studies tested whether NPY treatment induces stress resilience by modulating NPY (10 pmol) was delivered daily for 5 d bilaterally into the BLA to induce resilience; thereafter, the electrophysiological properties of PNs and the expression of in the BLA were characterized.

Modulation of distal calcium electrogenesis by neuropeptide Y₁ receptors inhibits neocortical long-term depression.

In layer 5 neocortical pyramidal neurons, backpropagating action potentials (bAPs) firing at rates above a critical frequency (CF) induce supralinear Ca²⁺ influx and regenerative potentials in apical dendrites. Paired temporally with an EPSP, this Ca²⁺ influx can result in synaptic plasticity. We studied the actions of neuropeptide Y (NPY), an abundant neocortical neuropeptide, on Ca²⁺ influx in layer 5 pyramidal neurons of somatosensory neocortex in Sprague Dawley and Wistar rats, using a combination of somatic and dendritic intracellular recordings and simultaneous Ca²⁺ imaging.

Magel2 is required for leptin-mediated depolarization of POMC neurons in the hypothalamic arcuate nucleus in mice.

Prader-Willi Syndrome is the most common syndromic form of human obesity and is caused by the loss of function of several genes, including MAGEL2. Mice lacking Magel2 display increased weight gain with excess adiposity and other defects suggestive of hypothalamic deficiency. We demonstrate Magel2-null mice are insensitive to the anorexic effect of peripherally administered leptin.