Changes in potassium channel modulation may underlie afterhyperpolarization plasticity in oxytocin neurons during late pregnancy.

Oxytocin (OT) neurons exhibit larger afterhyperpolarizations (AHPs) following spike trains during late pregnancy and lactation, times when these neurons fire in bursts and release more OT associated with labor and lactation. Calcium-dependent AHPs mediated by SK channels show this plasticity, and are reduced when the channel complex is phosphorylated by casein kinase 2 (CK2), and increased when dephosphorylated by protein phosphatase (PP)2A, by altering Ca sensitivity. We compared AHP currents in supraoptic OT neurons after CK2 inhibition with 4,5,6,7-tetrabromobenzotriazole (TBB), or PP1-PP2A inhibition with okadaic acid (OA), to determine the roles of these enzymes in AHP plasticity, focusing on the peak current at 100 ms representing the SK-mediated, medium AHP (I).

Phosphatidylinositol 4,5-bisphosphate (PIP ) modulates afterhyperpolarizations in oxytocin neurons of the supraoptic nucleus.

Key Points: Afterhyperpolarizations (AHPs) generated by repetitive action potentials in supraoptic magnocellular neurons regulate repetitive firing and spike frequency adaptation but relatively little is known about PIP 's control of these AHPs. We examined how changes in PIP levels affected AHPs, somatic [Ca ] , and whole cell Ca currents. Manipulations of PIP levels affected both medium and slow AHP currents in oxytocin (OT) neurons of the supraoptic nucleus.

Computational model predicts a role for ERG current in repolarizing plateau potentials in dopamine neurons: implications for modulation of neuronal activity.

Blocking the small-conductance (SK) calcium-activated potassium channel promotes burst firing in dopamine neurons both in vivo and in vitro. In vitro, the bursting is unusual in that spiking persists during the hyperpolarized trough and frequently terminates by depolarization block during the plateau. We focus on the underlying plateau potential oscillation generated in the presence of both apamin and TTX, so that action potentials are not considered.

Molecular mimicry: cross-reactive antibodies from patients with immune-mediated neurologic disease inhibit neuronal firing.

Recent data indicate that molecular mimicry may play a role in the pathogenesis of human-T-lymphotropic virus type-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), an immune-mediated disease of the central nervous system (CNS). Specifically, HAM/TSP patients developed antibodies that cross-react with heterogeneous nuclear ribonuclear protein A1 (hnRNP A1), an antigen highly expressed in neurons. Antibodies to HTLV-1-tax cross-reacted with hnRNP A1, suggesting molecular mimicry between the two proteins.

Removal of GABAergic inhibition alters subthreshold input in neurons in forepaw barrel subfield (FBS) in rat first somatosensory cortex (SI) after digit stimulation.

Our objective was to test the hypothesis that suppression of GABAergic inhibition results in an enhancement of responses to stimulation of the surround receptive field. Neurons in the forepaw barrel subfield (FBS) in rat first somatosensory cortex (SI) receive short latency suprathreshold input from a principal location on the forepaw and longer latency subthreshold input from surrounding forepaw skin regions. Input from principal and surround receptive field sites was examined before, during, and after administration of the GABA(A) receptor blocker bicuculline methiodide (BMI) (in 165 mM NaCl at pH 3.

Autoimmunity due to molecular mimicry as a cause of neurological disease.

One hypothesis that couples infection with autoimmune disease is molecular mimicry. Molecular mimicry is characterized by an immune response to an environmental agent that cross-reacts with a host antigen, resulting in disease. This hypothesis has been implicated in the pathogenesis of diabetes, lupus and multiple sclerosis (MS).