Depression is a major public health problem for which the majority of patients are not effectively treated. This problem is exacerbated further in children and adolescents for whom only two antidepressant drugs are currently approved. Both belong to the selective serotonin (5-HT) reuptake inhibitor (SSRI) class of antidepressant, and act by blocking high-affinity uptake of 5-HT from extracellular fluid via the serotonin transporter(SERT).

During gestation, the excitatory neurotransmitter serotonin (5-hydroxytryptamine or 5-HT) directs synapse formation and pruning in fetal brain circuits responsible for shaping social behavior. This course of development continues to unfold after birth and with social stimulation, both in juvenile mice and in infants. The 5-HT neurotransmitter system, including its transporters and receptors, are among the earliest to appear in the brain during embryonic development. Critically, this occurs even before the fetal brain has neurons capable of producing 5-HT on their own.

Chemotherapy-induced peripheral neuropathy (CIPN) and the associated pain represent a clinically relevant limit to patient treatment with anti-cancerdrugs. Currently, there is no effective treatment for CIPN. Enhanced excitability of peripheral sensory neurons is thought to contribute to the generation and progression of CIPN. By directly affecting membrane excitability, CIPN-causing chemotherapy drugs may enhance neuronal activity eventuating neuroexcitotoxicity and neuropathy.

Abuse of prescription opioids had reached epidemic levels and is responsible for increasing emergency department visits and overdose deaths. Most prescription opioid deaths involve at least one other drug, often a benzodiazepine (BZD). Up to 70% of opioid abusers also use BZDs, reportedly to enhance opioid-induced feelings of euphoria. Coabuse of opioids and BZDs increases the risk of physical dependence and overdose, and studies in humans suggest that BZD enhancement of abuse-related effects of opioids occurs in dependent, and not in nondependent, individuals.

Basic Research

The past 5 years have seen a dramatic increase in the abuse of synthetic cathinones (e.g., MDPV and methylone), which are marketed as 'bath salts,' and are widely available for purchase on the internet and in local shops as 'safe' and 'legal highs.' In addition to a high potential for abuse, 'bath salts' also have a high potential fr toxicity, characterized by severe cardiovascular and neuropsychiatric complications.

Biophysical interactions of PIP2 and calmodulin with KCNQ (Kv7) K ion channels + KCNQ potassium channels control cellular excitability, and inherited mutations in the proximal half of the C- terminus of these membrane proteins can result in cardiac arrhythmia, deafness and epilepsy. The signature 'M-current' produced by KCNQ channels was first observed in sympathetic neurons, and can be inhibited by stimulation of Gq/11 muscarinic receptors.

Basic Research

Basic Research

Intricate molecular interactions between neurons and supporting glia cells are essential for the rapid propagation of action potentials and form the basis for myelinated axons to achieve saltatory conduction. Previously, the cell surface adhesion molecule Neurofascin (Nfasc) has been shown to have a dual-role, essential to the establishment of axonal domains from both the glial and neuronal interface.