TRPV1 and Osmoregulation
Sorana Ciura and Charles W. Bourque
(see pages 9069–9075)
Central control of systemic osmoregulation is the job of the organum vasculosum lamina terminalis (OVLT), located at the rostral ventral edge of the third ventricle. In this week’s Journal, Ciura and Bourque demonstrate that OVLT neurons are intrinsically osmosensitive because they express transient receptor potential vanilloid 1 (TRPV1) channels. The authors compared the neuronal activity of hypothalamic explants from wild-type and TRPV1-deficient mice. OVLT neurons in wild-type mice responded to increased osmolality with an increased firing rate, whereas TRPV1−/− neurons did not. OVLT neurons responded directly to the change in osmolality with membrane depolarization. Ruthenium red, a blocker of nonselective cation channels, prevented hypertonic solution-induced depolarization, pointing to TRPV1 as the transducer. In vivo, TRPV1−/− mice drank less water after an osmotic challenge than did their WT counterparts, placing TRPV1 in the pathway that triggers thirst.
Astrocyte Processes and Dendritic Spines in Motion
Michael Haber, Lei Zhou, and Keith K. Murai
(see pages 8881–8891)
Glial cells sure aren’t what they were thought to be. They have calcium signals, release transmitters, and receive “synaptic” input. Now Haber et al. provide evidence that they can even move faster than neurons. The authors used time-lapse confocal imaging of organotypic hippocampal explants to monitor the movements of dendritic spines and their associated glial processes. Two Semliki Forest viral vectors were used to selectively infect glia and neurons with membrane-tethered enhanced green fluorescent protein and red fluorescent protein. The membrane-tethered probes facilitated imaging of fine glial processes. In the hippocampal CA1 area, astrocytes and dendrites showed complex interactions, including astrocytic processes that encapsulated some dendritic spines. Astrocytic processes extended and retracted considerable distances (5 μm) during a 30 min observation period. The GABAA receptor antagonist bicuculline, which increases neural activity, stabilized spines but had no apparent effect on astrocyte motility. In general, interactions between astrocyte processes and larger spines were more stable than those with smaller spines. ⇓
To Burst or Not to Burst in the Medial Septum In Vivo
Axelle Pascale Simon, Frédérique Poindessous-Jazat, Patrick Dutar, Jacques Epelbaum, and Marie-Hélène Bassant
(see pages 9038–9046)
The neurons in the medial septum-diagonal band of Broca (MS-DB) have long been implicated in hippocampal theta rhythms. In this week’s Journal, Simon et al. sought to differentiate the firing patterns of GABAergic and cholinergic MS-DB neurons. Their results indicate that GABAergic cells rather than cholinergic neurons display theta-related bursting or tonic activity in the MS-DB. Parvalbumin (PV) labels most GABAergic septohippocampal neurons, whereas other GABAergic neurons express glutamic acid decarboxylase (GAD). The authors recorded from MS-DB neurons in anesthetized and unanesthetized rats, and labeled the recorded neurons with neurobiotin. Of 90 neurons, three-quarters expressed GAD, and PV labeled approximately one-third of those. Only eight neurons, negative for GAD and PV, were cholinergic. GABAergic neurons displayed tonic, cluster, or burst-firing discharge patterns that varied with the sleep–wake cycle, but PV-positive neurons displayed more pronounced rhythmic bursting activity. Cholinergic neurons all displayed a low discharge rate.
Neurobiology of Disease
A KCC2 Homolog and Seizures in Drosophila
Daria S. Hekmat-Scafe, Miriam Y. Lundy, Rakhee Ranga, and Mark A. Tanouye
(see pages 8943–8954)
By setting the chloride gradient across the membrane, the potassium/chloride cotransporter KCC2 controls whether GABAA receptor signaling in mammalian neurons is depolarizing or hyperpolarizing. In this week’s Journal, Hekmat-Scafe et al. explore the homologous K+/Cl− cotransporter in Drosophila. Null mutations in the kazachoc (kcc) gene were lethal, but partial loss-of-function mutations resulted in increased seizure sensitivity. Why the name kazachoc? Well, this is a Slavic dance that involves squatting and kicking, which reminded the authors of flies with the bang-sensitive (BS) phenotype, a behavior that correlates with seizure sensitivity. And what is a BS phenotype you ask? Well, flies are vortexed for 10 s at high speed, and BS-sensitive flies display a period of paralysis followed by hyperactivity. For kcc mutants, BS sensitivity showed incomplete penetrance and was more prominent at lower temperatures and younger ages. Kcc-related seizure susceptibility was also reduced in flies treated with the GABAA receptor antagonist picrotoxin and in flies that expressed reduced levels of the GABAA receptor.