Albumin induces excitatory synaptogenesis through astrocytic TGF-β/ALK5 signaling in a model of acquired epilepsy following blood-brain barrier dysfunction.

Post-injury epilepsy (PIE) is a common complication following brain insults, including ischemic, and traumatic brain injuries. At present, there are no means to identify the patients at risk to develop PIE or to prevent its development. Seizures can occur months or years after the insult, do not respond to anti-seizure medications in over third of the patients, and are often associated with significant neuropsychiatric morbidities.

AMPA receptor desensitization mutation results in severe developmental phenotypes and early postnatal lethality.

AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate) recep-tors desensitize rapidly and completely in the continued presence of their endogenous ligand glutamate; however, it is not clear what role AMPA receptor desensitization plays in the brain. We generated a knock-in mouse in which a single amino acid residue, which controls desensitization, was mutated in the GluA2 (GluR2) receptor subunit (GluA2(L483Y)). This mutation was homozygous lethal.

Synaptic circuit abnormalities of motor-frontal layer 2/3 pyramidal neurons in a mutant mouse model of Rett syndrome.

Motor and cognitive functions are severely impaired in Rett syndrome (RTT). Here, we examined local synaptic circuits of layer 2/3 (L2/3) pyramidal neurons in motor-frontal cortex of male hemizygous MeCP2-null mice at 3 to 4weeks of age. We mapped local excitatory input to L2/3 neurons using glutamate uncaging and laser scanning photostimulation, and compared synaptic input maps recorded from MeCP2-null and wild type (WT) mice.

Synaptic circuit abnormalities of motor-frontal layer 2/3 pyramidal neurons in an RNA interference model of methyl-CpG-binding protein 2 deficiency.

Rett syndrome, an autism spectrum disorder with prominent motor and cognitive features, results from mutations in the gene for methyl-CpG-binding protein 2 (MeCP2). Here, to identify cortical circuit abnormalities that are specifically associated with MeCP2 deficiency, we used glutamate uncaging and laser scanning photostimulation to survey intracortical networks in mouse brain slices containing motor-frontal cortex. We used in utero transfection of short hairpin RNA constructs to knock down MeCP2 expression in a sparsely distributed subset of layer (L) 2/3 pyramidal neurons in wild-type mice, and compared input maps recorded from transfected-untransfected pairs of neighboring neurons.

Local-Circuit Phenotypes of Layer 5 Neurons in Motor-Frontal Cortex of YFP-H Mice.

Layer 5 pyramidal neurons comprise an important but heterogeneous group of cortical projection neurons. In motor-frontal cortex, these neurons are centrally involved in the cortical control of movement. Recent studies indicate that local excitatory networks in mouse motor-frontal cortex are dominated by descending pathways from layer 2/3 to 5.

Top-down laminar organization of the excitatory network in motor cortex.

Cortical layering is a hallmark of the mammalian neocortex and a major determinant of local synaptic circuit organization in sensory systems. In motor cortex, the laminar organization of cortical circuits has not been resolved, although their input-output operations are crucial for motor control. Here, we developed a general approach for estimating layer-specific connectivity in cortical circuits and applied it to mouse motor cortex.

The role of the basal ganglia and cerebellum in language processing.

The roles of the cerebellum and basal ganglia have typically been confined in the literature to motor planning and control. However, mounting evidence suggests that these structures are involved in more cognitive domains such as language processing. In the current study, we looked at effective connectivity (the influence that one brain region has on another) of the cerebellum and basal ganglia with regions thought to be involved in phonological processing, i.