Correcting deregulated Fxyd1 expression rescues deficits in neuronal arborization and potassium homeostasis in MeCP2 deficient male mice.

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the MECP2 gene. In the absence of MeCP2, expression of FXYD domain-containing transport regulator 1 (FXYD1) is deregulated in the frontal cortex (FC) of mice and humans. Because Fxyd1 is a membrane protein that controls cell excitability by modulating Na, K-ATPase activity (NKA), an excess of Fxyd1 may reduce NKA activity and contribute to the neuronal phenotype of Mecp2 deficient (KO) mice.

A Glutamate Homeostat Controls the Presynaptic Inhibition of Neurotransmitter Release.

We have interrogated the synaptic dialog that enables the bi-directional, homeostatic control of presynaptic efficacy at the glutamatergic Drosophila neuromuscular junction (NMJ). We find that homeostatic depression and potentiation use disparate genetic, induction, and expression mechanisms. Specifically, homeostatic potentiation is achieved through reduced CaMKII activity postsynaptically and increased abundance of active zone material presynaptically at one of the two neuronal subtypes innervating the NMJ, while homeostatic depression occurs without alterations in CaMKII activity and is expressed at both neuronal subtypes.

Distributed representation of pelvic floor muscles in human motor cortex.

Human motor cortex can activate pelvic floor muscles (PFM), but the motor cortical representation of the PFM is not well characterized. PFM representation is thought to be focused in the supplementary motor area (SMA). Here we examine the degree to which PFM representation is distributed between SMA and the primary motor cortex (M1), and how this representation is utilized to activate the PFM in different coordination patterns.

A Presynaptic Glutamate Receptor Subunit Confers Robustness to Neurotransmission and Homeostatic Potentiation.

Homeostatic signaling systems are thought to interface with other forms of plasticity to ensure flexible yet stable levels of neurotransmission. The role of neurotransmitter receptors in this process, beyond mediating neurotransmission itself, is not known. Through a forward genetic screen, we have identified the Drosophila kainate-type ionotropic glutamate receptor subunit DKaiR1D to be required for the retrograde, homeostatic potentiation of synaptic strength.

Emerging links between homeostatic synaptic plasticity and neurological disease.

Homeostatic signaling systems are ubiquitous forms of biological regulation, having been studied for hundreds of years in the context of diverse physiological processes including body temperature and osmotic balance. However, only recently has this concept been brought to the study of excitatory and inhibitory electrical activity that the nervous system uses to establish and maintain stable communication. Synapses are a primary target of neuronal regulation with a variety of studies over the past 15 years demonstrating that these cellular junctions are under bidirectional homeostatic control.

Subunit-dependent postsynaptic expression of kainate receptors on hippocampal interneurons in area CA1.

Kainate receptors (KARs) contribute to postsynaptic excitation in only a select subset of neurons. To define the parameters that specify the postsynaptic expression of KARs, we examined the contribution of KARs to EPSCs on hippocampal interneurons in area CA1. Interneurons in stratum radiatum/lacunosum-moleculare express KARs both with and without the GluR5 subunit, but KAR-mediated EPSCs are generated mainly, if not entirely, by GluR5-containing KARs.

Anatomic distribution of reinforcer selective cell firing in the core and shell of the nucleus accumbens.

We have previously reported that distinct populations of nucleus accumbens (NAc) neurons differentially encode information about goal-directed behaviors for "natural" (food/water) vs. cocaine reinforcement [J Neurosci 20:4255-4266, (2000)]. Here, the anatomic distribution of reinforcer-selective cell firing was examined within the core and shell of the NAc.

Selective encoding of cocaine versus natural rewards by nucleus accumbens neurons is not related to chronic drug exposure.

We reported previously that subsets of nucleus accumbens (Acb) neurons differentially encode information about goal-directed behaviors for "natural" (food and water) versus cocaine reward in animals well trained to self-administer the drug (Carelli et al., 2000). Here, we examined whether repeated exposure to cocaine is the crucial determinate of the selective encoding of cocaine versus water reinforcement by Acb neurons.