Mapping thalamic innervation to individual L2/3 pyramidal neurons and modeling their 'readout' of visual input.

The thalamus is the main gateway for sensory information from the periphery to the mammalian cerebral cortex. A major conundrum has been the discrepancy between the thalamus's central role as the primary feedforward projection system into the neocortex and the sparseness of thalamocortical synapses. Here we use new methods, combining genetic tools and scalable tissue expansion microscopy for whole-cell synaptic mapping, revealing the number, density and size of thalamic versus cortical excitatory synapses onto individual layer 2/3 (L2/3) pyramidal cells (PCs) of the mouse primary visual cortex.

Selective ROCK2 Inhibition In Focal Cerebral Ischemia.

Objective: Rho-associated kinase (ROCK) is a key regulator of numerous processes in multiple cell types relevant in stroke pathophysiology. ROCK inhibitors have improved outcome in experimental models of acute ischemic or hemorrhagic stroke. However, the relevant ROCK isoform (ROCK1 or ROCK2) in acute stroke is not known.

Function of dopamine transporter is compromised in DYT1 transgenic animal model in vivo.

Early onset torsion dystonia (DYT1), the most common form of hereditary primary dystonia, is caused by a mutation in the TOR1A gene, which codes for the protein, torsinA. We previously examined the effect of the human mutant torsinA on striatal dopaminergic function in a conventional transgenic mouse model of DYT1 dystonia (hMT1), in which human mutant torsinA is expressed under the cytomegalovirus promotor. Systemic administration of amphetamine did not increase dopamine (DA) release as efficiently in these mice as compared with wild-type transgenic and non-transgenic mice.

Plasma and brain concentrations of oral therapeutic doses of methylphenidate and their impact on brain monoamine content in mice.

Methylphenidate is a frequently prescribed stimulant for the treatment of attention deficit hyperactivity disorder (ADHD). An important assumption in the animal models that have been employed to study methylphenidate's effects on the brain and behavior is that bioavailability of methylphenidate in the animal models reflects that in human subjects. From this perspective, the dose and route of administration of methylphenidate assume critical importance because both these factors likely influence rate of uptake, plasma and brain concentrations of the drug.

Dopamine release is impaired in a mouse model of DYT1 dystonia.

Early onset torsion dystonia, the most common form of hereditary primary dystonia, is caused by a mutation in the TOR1A gene, which codes for the protein torsinA. This form of dystonia is referred to as DYT1. We have used a transgenic mouse model of DYT1 dystonia [human mutant-type (hMT)1 mice] to examine the effect of the mutant human torsinA protein on striatal dopaminergic function.