Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes.

Muskelin (Mkln1) is implicated in neuronal function, regulating plasma membrane receptor trafficking. However, its influence on intrinsic brain activity and corresponding behavioral processes remains unclear. Here we show that murine Mkln1 knockout causes non-habituating locomotor activity, increased exploratory drive, and decreased locomotor response to amphetamine.

The Microtubule Severing Protein Katanin Regulates Proliferation of Neuronal Progenitors in Embryonic and Adult Neurogenesis.

Microtubule severing regulates cytoskeletal rearrangement underlying various cellular functions. Katanin, a heterodimer, consisting of catalytic (p60) and regulatory (p80) subunits severs dynamic microtubules to modulate several stages of cell division. The role of p60 katanin in the mammalian brain with respect to embryonic and adult neurogenesis is poorly understood.

Selective Inactivation of Reelin in Inhibitory Interneurons Leads to Subtle Changes in the Dentate Gyrus But Leaves Cortical Layering and Behavior Unaffected.

Reelin is an extracellular matrix protein, known for its dual role in neuronal migration during brain development and in synaptic plasticity at adult stages. During the perinatal phase, Reelin expression switches from Cajal-Retzius (CR) cells, its main source before birth, to inhibitory interneurons (IN), the main source of Reelin in the adult forebrain. IN-derived Reelin has been associated with schizophrenia and temporal lobe epilepsy; however, the functional role of Reelin from INs is presently unclear.

Disturbed Prefrontal Cortex Activity in the Absence of Schizophrenia-Like Behavioral Dysfunction in Deficient Mice.

, an activity regulated immediate early gene, is essential for learning and memory, synaptic plasticity, and maturation of neural networks. It has also been implicated in several neurodevelopmental disorders, including schizophrenia. Here, we used male and female constitutive and conditional knock-out (KO) mice to investigate the causal relationship between deletion and schizophrenia-linked neurophysiological and behavioral phenotypes.

Muskelin Coordinates PrP Lysosome versus Exosome Targeting and Impacts Prion Disease Progression.

Cellular prion protein (PrP) modulates cell adhesion and signaling in the brain. Conversion to its infectious isoform causes neurodegeneration, including Creutzfeldt-Jakob disease in humans. PrP undergoes rapid plasma membrane turnover and extracellular release via exosomes.

Neurobeachin and the Kinesin KIF21B Are Critical for Endocytic Recycling of NMDA Receptors and Regulate Social Behavior.

Autism spectrum disorders (ASDs) are associated with mutations affecting synaptic components, including GluN2B-NMDA receptors (NMDARs) and neurobeachin (NBEA). NBEA participates in biosynthetic pathways to regulate synapse receptor targeting, synaptic function, cognition, and social behavior. However, the role of NBEA-mediated transport in specific trafficking routes is unclear.

The Kinesin KIF21B Regulates Microtubule Dynamics and Is Essential for Neuronal Morphology, Synapse Function, and Learning and Memory.

The kinesin KIF21B is implicated in several human neurological disorders, including delayed cognitive development, yet it remains unclear how KIF21B dysfunction may contribute to pathology. One limitation is that relatively little is known about KIF21B-mediated physiological functions. Here, we generated Kif21b knockout mice and used cellular assays to investigate the relevance of KIF21B in neuronal and in vivo function.

Radixin regulates synaptic GABAA receptor density and is essential for reversal learning and short-term memory.

Neurotransmitter receptor density is a major variable in regulating synaptic strength. Receptors rapidly exchange between synapses and intracellular storage pools through endocytic recycling. In addition, lateral diffusion and confinement exchanges surface membrane receptors between synaptic and extrasynaptic sites.

Molecular and behavioral changes associated with adult hippocampus-specific SynGAP1 knockout.

The synaptic Ras/Rap-GTPase-activating protein (SynGAP1) plays a unique role in regulating specific downstream intracellular events in response to N-methyl-D-aspartate receptor (NMDAR) activation. Constitutive heterozygous loss of SynGAP1 disrupts NMDAR-mediated physiological and behavioral processes, but the disruptions might be of developmental origin. Therefore, the precise role of SynGAP1 in the adult brain, including its relative functional significance within specific brain regions, remains unexplored.

Disruption of hippocampus-regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP.

The brain-specific Ras/Rap-GTPase activating protein (SynGAP) is a prime candidate linking N-methyl-d-aspartate receptors to the regulation of the ERK/MAP kinase signalling cascade, suggested to be essential for experience-dependent synaptic plasticity. Here, we evaluated the behavioural phenotype of SynGAP heterozygous knockout mice (SG(+/-)), expressing roughly half the normal levels of SynGAP. In the cognitive domain, SG(+/-) mice demonstrated severe working and reference memory deficits in the radial arm maze task, a mild impairment early in the transfer test of the water maze task, and a deficiency in spontaneous alternation in an elevated T-maze.

Appetitively motivated instrumental learning in SynGAP heterozygous knockout mice.

The synaptic Ras/Rap-GTPase-activating protein (SynGAP) regulates specific intracellular events following N-methyl-d-aspartate receptor (NMDAR) activation. Here, the impact of SynGAP heterozygous knockout (SG+/-) on NMDAR-dependent functions was assessed using different positive reinforcement schedules in instrumental conditioning. The knockout did not affect the temporal control of operant responding under a fixed interval (FI) schedule, but led to a putative enhancement in response vigor and/or disinhibition.

Age-related accumulation of Reelin in amyloid-like deposits.

Accumulating evidence suggest that alterations in Reelin-mediated signaling may contribute to neuronal dysfunction associated with Alzheimer's disease (AD), the most common form of senile dementia. However, limited information is available on the effect of age, the major risk factor of AD, on Reelin expression. Here, we report that normal aging in rodents and primates is accompanied by accumulation of Reelin-enriched proteinous aggregates in the hippocampal formation that are related to the loss of Reelin-expressing neurons.