A neurodevelopmental disorder caused by a dysfunctional allele.

P/Q-type Ca flux into nerve terminals Ca2.1 channels is essential for neurotransmitter release at neuromuscular junctions and nearly all central synapses. Mutations in , the gene encoding Ca2.

Advances in Ca1.1 gating: New insights into permeation and voltage-sensing mechanisms.

The Ca1.1 voltage-gated Ca channel carries L-type Ca current and is the voltage-sensor for excitation-contraction (EC) coupling in skeletal muscle. Significant breakthroughs in the EC coupling field have often been close on the heels of technological advancement.

Complex effects on Ca2.1 channel gating caused by a CACNA1A variant associated with a severe neurodevelopmental disorder.

P/Q-type Ca currents mediated by Ca2.1 channels are essential for active neurotransmitter release at neuromuscular junctions and many central synapses. Mutations in CACNA1A, the gene encoding the principal Ca2.

Promotion of corticospinal tract growth by KLF6 requires an injury stimulus and occurs within four weeks of treatment.

Axons in the corticospinal tract (CST) display a limited capacity for compensatory sprouting after partial spinal injuries, potentially limiting functional recovery. Forced expression of a developmentally expressed transcription factor, Krüppel-like factor 6 (KLF6), enhances axon sprouting by adult CST neurons. Here, using a pyramidotomy model of injury in adult mice, we confirm KLF6's pro-sprouting properties in spared corticospinal tract neurons and show that this effect depends on an injury stimulus.

Optogenetic Interrogation of Functional Synapse Formation by Corticospinal Tract Axons in the Injured Spinal Cord.

Unlabelled: To restore function after injury to the CNS, axons must be stimulated to extend into denervated territory and, critically, must form functional synapses with appropriate targets. We showed previously that forced overexpression of the transcription factor Sox11 increases axon growth by corticospinal tract (CST) neurons after spinal injury. However, behavioral outcomes were not improved, raising the question of whether the newly sprouted axons are able to form functional synapses.

The tumor suppressor HHEX inhibits axon growth when prematurely expressed in developing central nervous system neurons.

Neurons in the embryonic and peripheral nervous system respond to injury by activating transcriptional programs supportive of axon growth, ultimately resulting in functional recovery. In contrast, neurons in the adult central nervous system (CNS) possess a limited capacity to regenerate axons after injury, fundamentally constraining repair. Activating pro-regenerative gene expression in CNS neurons is a promising therapeutic approach, but progress is hampered by incomplete knowledge of the relevant transcription factors.

Increased prefrontal cortex neurogranin enhances plasticity and extinction learning.

Increasing plasticity in neurons of the prefrontal cortex (PFC) has been proposed as a possible therapeutic tool to enhance extinction, a process that is impaired in post-traumatic stress disorder, schizophrenia, and addiction. To test this hypothesis, we generated transgenic mice that overexpress neurogranin (a calmodulin-binding protein that facilitates long-term potentiation) in the PFC. Neurogranin overexpression in the PFC enhanced long-term potentiation and increased the rates of extinction learning of both fear conditioning and sucrose self-administration.

Levels of Ca(V)1.2 L-Type Ca(2+) Channels Peak in the First Two Weeks in Rat Hippocampus Whereas Ca(V)1.3 Channels Steadily Increase through Development.

Influx of calcium through voltage-dependent channels regulates processes throughout the nervous system. Specifically, influx through L-type channels plays a variety of roles in early neuronal development and is commonly modulated by G-protein-coupled receptors such as GABA(B) receptors. Of the four isoforms of L-type channels, only Ca(V)1.

Sickle cell mice exhibit mechanical allodynia and enhanced responsiveness in light touch cutaneous mechanoreceptors.

Background: Sickle cell disease (SCD) is associated with both acute vaso-occlusive painful events as well as chronic pain syndromes, including heightened sensitivity to touch. We have previously shown that mice with severe SCD (HbSS mice; express 100% human sickle hemoglobin in red blood cells; RBCs) have sensitized nociceptors, which contribute to increased mechanical sensitivity. Yet, the hypersensitivity in these neural populations alone may not fully explain the mechanical allodynia phenotype in mouse and humans.