The ventral pallidum (VP) lies at the interface between sensory, motor, and cognitive processing—with a particular role in mounting behavioral responses to rewards. Though the VP is predominantly GABAergic, glutamate neurons were recently identified, though their relative abundances and respective roles are unknown. Here, we show that VP glutamate neurons are concentrated in the rostral ventromedial VP and project to qualitatively similar targets as do VP GABA neurons. At the functional level, we used optogenetics to show that activity in VP GABA neurons can drive positive reinforcement, particularly through projections to the ventral tegmental area (VTA). On the other hand, activation of VP glutamate neurons leads to behavioral avoidance, particularly through projections to the lateral habenula. These findings highlight cell-type and projection-target specific roles for VP neurons in behavioral reinforcement, dysregulation of which could contribute to the emergence of negative symptoms associated with drug addiction and other neuropsychiatric disease.
In addition to dopamine neurons, the ventral tegmental area (VTA) contains GABA-, glutamate- and co-releasing neurons, and recent reports suggest a complex role for the glutamate neurons in behavioural reinforcement. We report that optogenetic stimulation of VTA glutamate neurons or terminals serves as a positive reinforcer on operant behavioural assays. Mice display marked preference for brief over sustained VTA glutamate neuron stimulation resulting in behavioural responses that are notably distinct from dopamine neuron stimulation and resistant to dopamine receptor antagonists. Whole-cell recordings reveal EPSCs following stimulation of VTA glutamate terminals in the nucleus accumbens or local VTA collaterals; but reveal both excitatory and monosynaptic inhibitory currents in the ventral pallidum and lateral habenula, though the net effects on postsynaptic firing in each region are consistent with the observed rewarding behavioural effects. These data indicate that VTA glutamate neurons co-release GABA in a projection-target-dependent manner and that their transient activation drives positive reinforcement.
The ventral tegmental area (VTA) plays a central role in the neural circuit control of behavioral reinforcement. Though considered a dopaminergic nucleus, the VTA contains substantial heterogeneity in neurotransmitter type, containing also GABA and glutamate neurons. Here we used a combinatorial viral approach to transsynaptically label afferents to defined VTA dopamine, GABA, or glutamate neurons. Surprisingly, we find that these populations received qualitatively similar inputs, with dominant and comparable projections from the lateral hypothalamus, raphe, and ventral pallidum. However, notable differences were observed with striatal regions and globus pallidus providing a greater share of input to VTA dopamine neurons, cortical input preferentially on to glutamate neurons, and GABA neurons receiving proportionally more input from the lateral habenula and laterodorsal tegmental nucleus. By comparing inputs to each of the transmitter-defined VTA cell types this study sheds important light on the systems-level organization of diverse inputs to VTA.
Background and PurposeᄏBenign paroxysmal positional vertigo (BPPV) is the most common form of vertigo. Although the repositioning maneuver dramatically improves the vertigo, some patients complain of residual dizziness. We evaluated the incidence and characteristics of persistent dizziness after successful particle repositioning and the clinical factors associated with the residual dizziness.MethodsᄏWe performed a prospective investigation in 49 consecutive patients with confirmed BPPV. The patients were treated with a repositioning maneuver appropriate for the type of BPPV. Success was defined by the resolution of nystagmus and positional vertigo. All patients were followed up until complete resolution of all dizziness, for a maximum of 3 months. We collected data on the characteristics and duration of any residual dizziness and analyzed the clinical factors associated with the residual dizziness.ResultsᄏOf the 49 patients, 11 were men and 38 were women aged 60.4±13.0 years (mean ±SD), and 30 (61%) of them complained of residual dizziness after successful repositioning treatment. There were two types of residual dizziness: continuous lightheadedness and shortlasting unsteadiness occurring during head movement, standing, or walking. The dizziness lasted for 16.4±17.6 days (range=2-80 days, median=10 days). A longer duration of BPPV before treatment was significantly associated with residual dizziness (p=0.04).ConclusionsᄏResidual dizziness after successful repositioning was observed in two-thirds of the patients with BPPV and disappeared within 3 months without specific treatment in all cases. The results indicate that early successful repositioning can reduce the incidence of residual dizziness.
Oxidation-resistant copper nanowires (Cu NWs) are synthesized by a polyol reduction method. These Cu NWs show excellent oxidation resistance, good dispersibility, and have a low sintering temperature. A Cu NW-based flexible, foldable, and free-standing electrode is fabricated by filtration and a sintering process. The electrode also exhibits high electrical conductivity even bending, folding, and free-standing.
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