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Giant, aspiny cholinergic interneurons (ChIs) have long been known to be key nodes in the striatal circuitry controlling goal-directed actions and habits. In recent years, new experimental approaches, like optogenetics and monosynaptic rabies virus mapping, have expanded our understanding of how ChIs contribute to the striatal activity underlying action selection and the interplay of dopaminergic and cholinergic signaling. These approaches also have begun to reveal how ChI function is distorted in disease states affecting the basal ganglia, like Parkinson's disease (PD). This review gives a brief overview of our current understanding of the functional role played by ChIs in striatal physiology and how this changes in PD. The translational implications of these discoveries, as well as the gaps that remain to be bridged, are discussed as well.

A simple model to predict hurricane intensity based on energetics is described and tested. It is assumed that future hurricane intensity is solely determined by the large-scale environmental conditions and the present state of the hurricane, implying that subscale processes, if important, are strongly conditioned by the environment. It is also assumed that the hurricane track and the large-scale environmental conditions that are used as inputs to the intensity model can be reasonably predicted by comprehensive numerical models. A series of runs starting from different times are performed. The results by the model are fairly consistent with observations. The intensity sensitivity to various factors and parameters used in the model is also discussed. Copyright © 2005 Royal Meteorological Society

This article describes an approach to hurricane potential intensity with a model that considers total kinetic energy balance within a hurricane. The major kinetic energy source and sink are the kinetic energy converted from sea surface entropy flux and the surface dissipation, respectively, but the conversion efficiency is radius-dependent in this model. Also, the internal conversion due to convectively available potential energy (CAPE) as a source is considered. In contrast to previous potential intensity models, energy balance in the entire hurricane is used to get its steady state. With this model, the roles of environmental sea surface temperature (SST), CAPE and some features of the hurricane itself in determining hurricane potential intensity are investigated. The results indicate that existence of CAPE may lead to the steady state (or potential intensity) appreciably different from the otherwise surface entropy flux conversion and surface dissipation balanced state, although CAPE contribution to kinetic energy generation is usually much smaller than that of the surface flux. It is interesting that hurricane potential intensity seems less dependent on the underlying SST than was shown with previous theoretical models. The results also suggest that hurricane size may affect its potential intensity in that larger-sized hurricanes tend to have higher potential intensities. Copyright © 2004 Royal Meteorological Society

Pregnenolone sulphate (PREGS) has generated interest as one of the most potent memory-enhancing neurosteroids to be examined in rodent learning studies, with particular importance in the ageing process. The mechanism by which this endogenous steroid enhances memory formation is hypothesized to involve actions on glutamatergic and GABAergic systems. This hypothesis stems from findings that PREGS is a potent positive modulator of N-methyl-d-aspartate receptors (NMDARs) and a negative modulator of gamma-aminobutyric acid(A) receptors (GABA(A)Rs). Moreover, PREGS is able to reverse the amnesic-like effects of NMDAR and GABA(A)R ligands. To investigate this hypothesis, the present study in rats examined the memory-altering abilities of structural analogs of PREGS, which differ in their modulation of NMDAR and/or GABA(A)R function. The analogs tested were: 11-ketopregnenolone sulphate (an agent that is inactive at GABA(A)Rs and NMDARs), epipregnanolone ([3beta-hydroxy-5beta-pregnan-20-one] sulphate, an inhibitor of both GABA(A)Rs and NMDARs), and a newly synthesized (-) PREGS enantiomer (which is identical to PREGS in effects on GABA(A)Rs and NMDARs). The memory-enhancing effects of PREGS and its analogs were tested in the passive avoidance task using the model of scopolamine-induced amnesia. Both PREGS and its (-) enantiomer blocked the effects of scopolamine. The results show that, unlike PREGS, 11-ketopregnenolone sulphate and epipregnanolone sulphate failed to block the effect of scopolamine, suggesting that altering the modulation of NMDA receptors diminishes the memory-enhancing effects of PREGS. Moreover, enantioselectivity was demonstrated by the ability of natural PREGS to be an order of magnitude more effective than its synthetic enantiomer in reversing scopolamine-induced amnesia. These results identify a novel neuropharmacological site for the modulation of memory processes by neuroactive steroids.

1. Under whole-cell voltage clamp, the effects of initial voltage conditions and membrane tension on gating charge and voltage-dependent capacitance were studied in human embryonic kidney cells (TSA201 cell line) transiently transfected with the gene encoding the gerbil protein prestin. Conformational changes in this membrane-bound protein probably provide the molecular basis of the outer hair cell (OHC) voltage-driven mechanical activity, which spans the audio spectrum. 2. Boltzmann characteristics of the charge movement in transfected cells were similar to those reported for OHCs (Q(max) = 0.99 +/- 0.16 pC, z = 0.88 +/- 0.02; n = 5, means +/- S.E.M.). Unlike that of the adult OHC, the voltage at peak capacitance (V(pkcm)) was very negative (-74.7 +/- 3.8 mV). Linear capacitance in transfected cells was 43.7 +/- 13.8 pF and membrane resistance was 458 +/- 123 Mohms. 3. Voltage steps from the holding potential preceding the measurement of capacitance-voltage functions caused a time- and voltage-dependent shift in V(pkcm). For a prepulse to -150 mV, from a holding potential of 0 mV, V(pkcm) shifted 6.4 mV, and was fitted by a single exponential time constant of 45 ms. A higher resolution analysis of this time course was made by measuring the change in capacitance during a fixed voltage step and indicated a double exponential shift (tau(0) = 51.6 ms, tau(1) = 8.5 s) similar to that of the native gerbil OHC. 4. Membrane tension, delivered by increasing pipette pressure, caused a positive shift in V(pkcm). A maximal shift of 7.5 mV was obtained with 2 kPa of pressure. The effect was reversible. 5. Our results show that the sensitivity of prestin to initial voltage and membrane tension, though present, is less than that observed in adult OHCs. It remains possible that some other interacting molecular species within the lateral plasma membrane of the native OHC amplifies the effect of tension and prior voltage on prestin's activity.

1. Muscarinic modulation of nicotinic transmission was studied in bullfrog sympathetic ganglia by recording synaptic currents from B and C neurones. 2. Bath-applied muscarine reduced the amplitude of EPSCs recorded at < 0.2 Hz from B neurones by up to 57%. The action was reversible, showed no apparent desensitization, and had an EC50 of 102 nM. Muscarine had no effect on EPSCs in C neurones. 3. Currents evoked by ionophoretic application of ACh to B neurones were unchanged by muscarine. Muscarine increased the coefficient of variation (c.v.) of EPSC amplitude. The effect upon the ratio of c.v.2control to c.v.2muscarine was proportional to the change in mean EPSC amplitude. 4. Activation of muscarinic receptors by ACh from nerve terminals was observed by comparing trains of EPSCs in normal Ringer solution and atropine. Inhibition of EPSC amplitude by 15-40% was seen as frequency was increased from 1 to 5 Hz. The minimal latency for onset of inhibition was approximately 2 s. Stimulation at 20 Hz did not produce inhibition. 5. The results indicate that presynaptic muscarinic receptors are selectively expressed by a functional subclass of preganglionic sympathetic nerve terminals. Physiological activation of the receptors occurs during repetitive activity. The extent of autoreceptor-mediated inhibition varies as a biphasic function of stimulus frequency.

1. The sensitivity of nicotinic synapses to alpha-bungarotoxin (alpha-Bgt) and neuronal-bungarotoxin (n-Bgt) was measured in the B and C cell systems of bullfrog paravertebral sympathetic ganglia 9 and 10 by recording extracellular compound postganglionic action potentials from the rami communicantes. 2. High concentrations (10 microM) of alpha-Bgt applied for up to 8 h had no effect upon synaptic transmission in either the B or C cell system. Ganglia pretreated with collagenase were also insensitive to alpha-Bgt. In control experiments on isolated sartorius muscle preparations, nerve-evoked twitches were fully blocked by 30-100 nM alpha-Bgt. 3. Nicotinic transmission in the B and C cell systems was reversibly blocked by 30-300 nM n-Bgt. Block appeared within 25-45 min of exposure to toxin and reversed fully with a half-time of 40-80 min. This was indistinguishable from washout times after block by 100 microM (+)-tubocurarine. 4. The results demonstrate close parallels between the bungarotoxin sensitivity of neuronal nicotinic receptors mediating ganglionic transmission in functional subclasses of bullfrog sympathetic neurones and the bungarotoxin sensitivity which has been reported for autonomic in avian and mammalian preparations.