Neuroscience
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Following a Pavlovian pairing procedure, alcohol-paired cues come to elicit behavioral responses that lead to alcohol consumption. Here we used an optogenetic approach to activate basolateral amygdala (BLA) axonal terminals targeting the shell of nucleus accumbens (AcbSh) and investigated a possible influence over cue-conditioned alcohol seeking and alcohol drinking, based on the demonstrated roles of these areas in behavioral responding to Pavlovian cues and in feeding behavior. Rats were trained to anticipate alcohol or sucrose following the onset of a discrete conditioned stimulus (CS). ⋯ Finally, the suppressive effect of photoactivation on cued-triggered seeking was also evidenced in animals trained with sucrose. Together these findings suggest that photoactivation of BLA terminals in the AcbSh can override the conditioned motivational properties of reward-predictive cues as well as unconditioned consummatory responses necessary for alcohol drinking. The findings provide evidence for a limbic-striatal influence over motivated behavior for orally consumed rewards, including alcohol.
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Macrophage migration inhibitory factor (MIF) plays an important role in hearing function; however, the underlying mechanism remains indistinct. PVM/Ms from the stria vascularis of lateral wall of cochlea in young and aged mice were isolated, and the mRNA and protein expression levels were detected. MIF was knocked down or overexpresssed in vitro, and transfection was performed in vivo. ⋯ Moreover, MIF effectively altered the expression levels of CDK1, BRAF, p-ERK1/2, p-PI3K, and p-Akt. Furthermore, ERK inhibitor PD98059 or PI3K inhibitor LY294002 significantly reversed the effects of Si-MIF on PVM/Ms from young mice, whereas ERK activator EGF or PI3K activator IGF significantly reversed the effects of Ad-MIF on PVM/Ms from aged mice. Taken together, MIF mediates the viability and apoptosis of PVM/Ms, at least partially, through MAPK and/or PI3K/Akt pathway.
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Neural populations produce complex oscillatory patterns thought to implement brain function. The dominant rhythm in the healthy adult human brain is formed by alpha oscillations with a typical power peak most commonly found between 8 and 12Hz. This alpha peak frequency has been repeatedly discussed as a highly heritable and stable neurophysiological "trait" marker reflecting anatomical properties of the brain, and individuals' general cognitive capacity. ⋯ Based on the converging experimental and theoretical results from numerous recent studies, here we propose that alpha frequency variability forms the basis of an adaptive mechanism mirroring the activation level of neural populations which has important functional implications. We here integrate experimental and computational perspectives to shed new light on the potential role played by shifts in alpha peak frequency and discuss resulting implications. We further propose a potential mechanism by which alpha oscillations are regulated in a noisy network of spiking neurons in presence of delayed feedback.
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Cholinergic interneurons provide rich local innervation of the striatum and play an important role in controlling behavior, as evidenced by the variety of movement and psychiatric disorders linked to disrupted striatal cholinergic transmission. Much progress has been made in recent years regarding our understanding of how these interneurons contribute to the processing of information in the striatum. In particular, investigation of the activity of presumed striatal cholinergic interneurons, identified as tonically active neurons or TANs in behaving animals, has pointed to their role in the signaling and learning of the motivational relevance of environmental stimuli. ⋯ Consequently, our current understanding of the function of cholinergic transmission in the striatum is challenged by the rapidly growing, but often confusing literature on the relationship between TAN activity and specific behaviors. As regards the precise nature of the information conveyed by the cholinergic TANs, a recent influential view emphasized that these local circuit neurons may play a special role in the processing of contextual information that is important for reinforcement learning and selection of appropriate actions. This review provides a summary of recent progress in TAN physiology from which it is proposed that striatal cholinergic interneurons are crucial elements for flexible switching of behaviors under changing environmental conditions.
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Although often examined in isolation, a single neuromodulator typically has multiple cellular and synaptic effects. Here, we have examined the interaction of the cellular and synaptic effects of 5-HT in the lamprey spinal cord. 5-HT reduces the amplitude of glutamatergic synaptic inputs and the slow post-spike afterhyperpolarization (sAHP) in motor neurons. We examined the interaction between these effects using ventral root activity evoked by stimulation of the spinal cord. ⋯ In these experiments, 5-HT reduced the ventral root response, presumably because the reduction of the synaptic input now dominated. This was supported by computer simulations that showed that the motor output could be maintained over a wide range of synaptic input values if they were matched by changes in postsynaptic excitability. The effects of 5-HT on ventral root responses were altered by spinal cord lesions: 5-HT significantly increased ventral root responses in animals that recovered good locomotor function, consistent with a lesion-induced reduction in the synaptic effects of 5-HT, which thus biases its effects to the increase in motor neuron excitability.