Calcium-induced calcium release activates spontaneous miniature outward currents in newt medullary reticular formation neurons.

Neurons in the medullary reticular formation are involved in the control of postural and locomotor behaviors in all vertebrates. Reticulospinal neurons in this brain region provide one of the major descending projections to the spinal cord. Although neurons in the newt medullary reticular formation have been extensively studied using in vivo extracellular recordings, little is known of their intrinsic biophysical properties or of the underlying circuitry of this region. Using whole cell patch-clamp recordings in brain slices containing the rostromedial reticular formation from adult male newts, we observed spontaneous miniature outward currents (SMOCs) in ~2/3 of neurons. Although SMOCs superficially resembled inhibitory postsynaptic currents (IPSCs), they had slower risetimes and decay times than spontaneous IPSCs. SMOCs required intracellular Ca2+ release from ryanodine receptors and were also dependent on the influx of extracellular Ca2+. SMOCs were unaffected by apamin but were partially blocked by iberiotoxin and charybdotoxin, indicating that SMOCs were mediated by big-conductance Ca2+-activated K+ channels. Application of the sarco/endoplasmic Ca2+ ATPase inhibitor cyclopiazonic acid blocked the generation of SMOCs and also increased neural excitability. Neurons with SMOCs had significantly broader action potentials, slower membrane time constants, and higher input resistance than neurons without SMOCs. Thus, SMOCs may serve as a mechanism to regulate action potential threshold in a majority of neurons within the newt medullary reticular formation. NEW & NOTEWORTHY The medullary reticular formation exerts a powerful influence on sensorimotor integration and subsequent motor behavior, yet little is known about the neurons involved. In this study, we identify a transient potassium current that regulates action potential threshold in a majority of medullary reticular neurons.

Lithium modulates cortical excitability in vitro.

The sometimes devastating mood swings of bipolar disorder are prevented by treatment with selected antiepileptic drugs, or with lithium. Abnormal membrane ion channel expression and excitability in brain neurons likely underlie bipolar disorder, but explaining therapeutic effects in these terms has faced an unresolved paradox: the antiepileptic drugs effective in bipolar disorder reduce Na(+) entry through voltage-gated channels, but lithium freely enters neurons through them. Here we show that lithium increases the excitability of output neurons in brain slices of the mouse olfactory bulb, an archetypical cortical structure. Treatment in vitro with lithium (1 to 10mM) depolarizes mitral cells, blocks action potential hyperpolarization, and modulates their responses to synaptic input. We suggest that Na(+) entry through voltage-gated channels normally directly activates K(+) channels regulating neuron excitability, but that at therapeutic concentrations, lithium entry and accumulation reduces this K(+) channel activation. The antiepileptic drugs effective in bipolar disorder and lithium may thus share a membrane target consisting of functionally coupled Na(+) and K(+) channels that together control brain neuron excitability.

All-or-none population bursts temporally constrain surround inhibition between mouse olfactory glomeruli.

With each sniff, the olfactory bulbs of the brain generate a neural activity pattern representing the odour environment, transmitting this to higher brain centres in the form of mitral cell output. Inhibitory circuits in the olfactory bulb glomerular and external plexiform layers may amplify contrast in these patterns, through surround inhibition of mitral cells. These circuits may operate in series, but their respective roles are unclear. A single sniff is sufficient for odour discrimination, but is not clear that the inhibitory circuits act within this timeframe. We used microdissected slices of mouse olfactory bulb to study each circuit in isolation. We found that unlike surround inhibition mediated in the external plexiform layer, surround inhibition mediated in the glomerular layer was activated by sensory synaptic input, but not by mitral cell output. The results also suggest that interactions between olfactory glomeruli are exclusively inhibitory, unlike in antennal lobe, and that surround inhibition mediated within the external plexiform layer may involve neural circuit elements not preserved in slice preparations. Surround inhibition was effective only after an interval corresponding to a single sniff in vivo. Surplus excitation, initiated by sensory input but generated by collective all-or-none responses of mitral cells, may delay surround inhibition and allow the synchronous activation of multiple glomeruli without each suppressing the other. Surround inhibition in the glomerular layer may subsequently allow a fresh representation of the odour environment to be generated with each sniff. These findings are consistent with combinatorial odour coding based on all-or-none glomerular responses.

Neuroanatomical distribution of cannabinoid receptor gene expression in the brain of the rough-skinned newt, Taricha granulosa.

Type I cannabinoid receptor (CB1) is a G-protein coupled receptor with a widespread distribution in the central nervous system in mammals. In a urodele amphibian, the rough-skinned newt (Taricha granulosa), recent evidence indicates that endogenous cannabinoids (endocannabinoids) mediate behavioral responses to acute stress and electrophysiological responses to corticosterone. To identify possible sites of action for endocannabinoids, in situ hybridization using a gene and species specific cRNA probe was used to label CB1 mRNA in brains of male T. granulosa. Labeling of CB1 mRNA in the telencephalon was observed in the olfactory bulb and all areas of the pallium, as well as the bed nucleus of the stria terminalis and nucleus amygdalae dorsolateralis. The labeling of CB1 mRNA was also found in regions of the preoptic area, thalamus, midbrain tegmentum and tectum, cerebellum, and the stratum griseum of the hindbrain. A notable difference in CB1 labeling between this amphibian and mammals is the abundance of labeling in areas associated with olfaction (anterior olfactory nuclei, nucleus amygdalae dorsolateralis, and lateral pallium), which hints that endocannabinoids might modulate responses to odors as well as pheromones. This widespread distribution of CB1 labeling, particularly in sensory and motor control centers, fits with prior results showing that endocannabinoids modulate sensorimotor processing and behavioral output in this species. The distribution of CB1 in the brain of T. granulosa was in many of the same sites previously observed in the brain of the anuran amphibian, Xenopus laevis, as well as those of different species of mammals, suggesting that endocannabinoid signaling pathways are conserved.