Severe and progressive neurotransmitter release aberrations in familial hemiplegic migraine type 1 Cacna1a S218L knock-in mice.

Familial hemiplegic migraine type 1 (FHM1) is caused by mutations in the CACNA1A gene, encoding neuronal presynaptic Ca(V)2.1 (P/Q-type) Ca(2+) channels. These channels mediate neurotransmitter release at many central synapses and at the neuromuscular junction (NMJ).

High cortical spreading depression susceptibility and migraine-associated symptoms in Ca(v)2.1 S218L mice.

Objective: The CACNA1A gene encodes the pore-forming subunit of neuronal Ca(V)2.1 Ca2+ channels. In patients, the S218L CACNA1A mutation causes a dramatic hemiplegic migraine syndrome that is associated with ataxia, seizures, and severe, sometimes fatal, brain edema often triggered by only a mild head trauma.

Automated segmentation of in vivo and ex vivo mouse brain magnetic resonance images.

Segmentation of magnetic resonance imaging (MRI) data is required for many applications, such as the comparison of different structures or time points, and for annotation purposes. Currently, the gold standard for automated image segmentation is nonlinear atlas-based segmentation. However, these methods are either not sufficient or highly time consuming for mouse brains, owing to the low signal to noise ratio and low contrast between structures compared with other applications.

Enhanced circadian phase resetting in R192Q Cav2.1 calcium channel migraine mice.

Objective: Mammalian circadian rhythms are driven by the circadian pacemaker of the suprachiasmatic nucleus (SCN) and are synchronized to the external 24-hour light/dark cycle. After advance time zone transitions (eastbound jet lag), overt circadian rhythms require several days to adjust. The retarded adaptation may protect against acute imbalance of different brain systems.

Reduced ACh release at neuromuscular synapses of heterozygous leaner Ca(v)2.1-mutant mice.

Episodic ataxia type 2 (EA2) is an autosomal dominantly inherited neurological disorder. Patients have CACNA1A gene mutations resulting in truncation or single amino acid changes in the pore-forming subunit of Ca(v)2.1 (P/Q-type) Ca(2+) channels.

T(1) relaxation in in vivo mouse brain at ultra-high field.

Accurate knowledge of relaxation times is imperative for adjustment of MRI parameters to obtain optimal signal-to-noise ratio (SNR) and contrast. As small animal MRI studies are extended to increasingly higher magnetic fields, these parameters must be assessed anew. The goal of this study was to obtain accurate spin-lattice (T(1)) relaxation times for the normal mouse brain at field strengths of 9.

Genetic models of migraine.

Migraine is a common, disabling, complex brain disorder, presenting in attacks that may have up to 3 phases: a prodromal phase, the aura phase, and the headache phase. The pathogenesis of the aura and headache phases is reasonably well understood, but the mechanism by which migraine attacks are triggered is unknown. Most likely, migraineurs have a genetically determined reduced threshold for migraine triggers.

Severely impaired neuromuscular synaptic transmission causes muscle weakness in the Cacna1a-mutant mouse rolling Nagoya.

The ataxic mouse rolling Nagoya (RN) carries a missense mutation in the Cacna1a gene, encoding the pore-forming subunit of neuronal Ca(v)2.1 (P/Q-type) Ca2+ channels. Besides being the predominant type of Ca(v) channel in the cerebellum, Ca(v)2.

Redundancy of Cav2.1 channel accessory subunits in transmitter release at the mouse neuromuscular junction.

Ca(v)2.1 (P/Q-type) channels possess a voltage-sensitive pore-forming alpha(1) subunit that can associate with the accessory subunits alpha(2)delta, beta and gamma. The primary role of Ca(v)2.

Conditional inactivation of the Cacna1a gene in transgenic mice.

Ca(v)2.1 (P/Q-type) voltage-gated calcium channels play an important role in neurotransmitter release at many brain synapses and at the neuromuscular junction. Mutations in the CACNA1A gene, encoding the pore forming alpha(1) subunit of Ca(v)2.

Compensatory contribution of Cav2.3 channels to acetylcholine release at the neuromuscular junction of tottering mice.

Tottering (Tg) mice carry the mutation P601L in their Cacna1a encoded Cav2.1 channels. Transmitter release at the wild-type neuromuscular junction (NMJ) is almost exclusively mediated by Cav2.

A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression.

Migraine is a common, disabling, multifactorial, episodic neurovascular disorder of unknown etiology. Familial hemiplegic migraine type 1 (FHM-1) is a Mendelian subtype of migraine with aura that is caused by missense mutations in the CACNA1A gene that encodes the alpha(1) subunit of neuronal Ca(v)2.1 Ca(2+) channels.