Long-term potentiation-dependent spine enlargement requires synaptic Ca2+-permeable AMPA receptors recruited by CaM-kinase I.

It is well established that long-term potentiation (LTP), a paradigm for learning and memory, results in a stable enlargement of potentiated spines associated with recruitment of additional GluA1-containing AMPA receptors (AMPARs). Although regulation of the actin cytoskeleton is involved, the detailed signaling mechanisms responsible for this spine expansion are unclear. Here, we used cultured mature hippocampal neurons stimulated with a glycine-induced, synapse-specific form of chemical LTP (GI-LTP).

Young age and low temperature, but not female gender delay ATP loss and glutamate release, and protect Purkinje cells during simulated ischemia in cerebellar slices.

Excessive activation of glutamate receptors contributes to Purkinje cell (PC) damage during brain ischemia, but the mechanisms of glutamate release are contentious. Age, gender and temperature all strongly influence ischemic brain damage, but the mechanisms underlying their influence are not fully understood. We determined how age, gender and temperature influence ATP loss, glutamate release, glutamate receptor activation and PC damage during cerebellar ischemia.

Astrocyte metabolism and signaling during brain ischemia.

Brain ischemia results from cardiac arrest, stroke or head trauma. These conditions can cause severe brain damage and are a leading cause of death and long-term disability. Neurons are far more susceptible to ischemic damage than neighboring astrocytes, but astrocytes have diverse and important functions in many aspects of ischemic brain damage.

The pharmacology of cyclic nucleotide-gated channels: emerging from the darkness.

Cyclic nucleotide-gated (CNG) ion channels play a central role in vision and olfaction, generating the electrical responses to light in photoreceptors and to odorants in olfactory receptors. These channels have been detected in many other tissues where their functions are largely unclear. The use of gene knockouts and other methods have yielded some information, but there is a pressing need for potent and specific pharmacological agents directed at CNG channels.

Interplay between PIP3 and calmodulin regulation of olfactory cyclic nucleotide-gated channels.

Phosphatidylinositol-3,4,5-trisphosphate (PIP3) has been proposed to modulate the odorant sensitivity of olfactory sensory neurons by inhibiting activation of cyclic nucleotide-gated (CNG) channels in the cilia. When applied to the intracellular face of excised patches, PIP3 has been shown to inhibit activation of heteromeric olfactory CNG channels, composed of CNGA2, CNGA4, and CNGB1b subunits, and homomeric CNGA2 channels. In contrast, we discovered that channels formed by CNGA3 subunits from cone photoreceptors were unaffected by PIP3.

Functional role of lipid raft microdomains in cyclic nucleotide-gated channel activation.

Cyclic nucleotide-gated (CNG) channels are the primary targets of light- and odorant-induced signaling in photoreceptors and olfactory sensory neurons. Compartmentalized cyclic nucleotide signaling is necessary to ensure rapid and efficient activation of these nonselective cation channels. However, relatively little is known about the subcellular localization of CNG channels or the mechanisms of their membrane partitioning.