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Dopamine neurons in the ventral tegmental area (VTA) represent a critical site of synaptic plasticity induced by addictive drugs. Orexin/hypocretin-containing neurons in the lateral hypothalamus project to the VTA, and behavioral studies have suggested that orexin neurons play an important role in motivation, feeding, and adaptive behaviors. However, the role of orexin signaling in neural plasticity...
Spontaneous network activity (SNA) has been described in most developing circuits, including the spinal cord, retina, and hippocampus. Despite the widespread nature of this developmental phenomenon, its role in network maturation is poorly understood. We reduced SNA in the intact embryo and found compensatory increases in synaptic strength of spinal motoneuron inputs. AMPAergic miniature postsynaptic...
Increased activity of D2 receptors (D2Rs) in the striatum has been linked to the pathophysiology of schizophrenia. To determine directly the behavioral and physiological consequences of increased D2R function in the striatum, we generated mice with reversibly increased levels of D2Rs restricted to the striatum. D2 transgenic mice exhibit selective cognitive impairments in working memory tasks and...
Microglia are the immune cells of the brain. Here we show a massive infiltration of highly ramified and elongated microglia within the core of amyloid plaques in transgenic mouse models of Alzheimer's disease (AD). Many of these cells originate from the bone marrow, and the β-amyloid-40 and -42 isoforms are able to trigger this chemoattraction. These newly recruited cells also exhibit a specific immune...
An essential step in Drosophila phototransduction is the hydrolysis of phosphatidylinositol 4,5 bisphosphate PI(4,5)P 2 by phospholipase Cβ (PLCβ) to generate a second messenger that opens the light-activated channels TRP and TRPL. Although the identity of this messenger remains unknown, recent evidence has implicated diacylglycerol kinase (DGK), encoded by rdgA, as a key enzyme that regulates...
The dopamine hypothesis of schizophrenia is based on evidence that the major antipsychotic drugs act by blocking dopamine D2 receptors and that dopamine-releasing drugs worsen symptoms. In this issue of Neuron, Kellendonk et al. report an elegant conditional transgenic mouse overexpressing dopamine D2 receptors selectively in the striatum. Strikingly, these animals display selective cognitive impairment...
Sequence disambiguation, the process by which overlapping sequences are kept separate, has been proposed to underlie a wide range of memory capacities supported by the hippocampus, including episodic memory and spatial navigation. We used functional magnetic resonance imaging (fMRI) to explore the dynamic pattern of hippocampal activation during the encoding of sequences of faces. Activation in right...
The formation and plasticity of synaptic connections rely on regulatory interactions between pre- and postsynaptic cells. We show that the Drosophila heparan sulfate proteoglycans (HSPGs) Syndecan (Sdc) and Dallylike (Dlp) are synaptic proteins necessary to control distinct aspects of synaptic biology. Sdc promotes the growth of presynaptic terminals, whereas Dlp regulates active zone form and function...
Nonsynaptic clusters of postsynaptic proteins have been documented; however, their role remains elusive. We monitored the trafficking of several candidate proteins implicated in synaptogenesis, when nonsynaptic clusters of scaffold proteins are most abundant. We find a protein complex consisting of two populations that differ in their content, mobility, and involvement in synapse formation. One subpopulation...
Many developing networks generate spontaneous network activity (SNA) that plays an important role in setting up functional circuitry, but how the proper level and pattern of SNA is itself maintained has not been clear. In this issue of Neuron, Gonzalez-Islas and Wenner show that SNA in the intact embryo regulates itself through a set of adaptive homeostatic plasticity mechanisms.
The molecular mechanisms that regulate the production and diversity of olfactory bulb interneurons remain poorly understood. With the exception of the GABAergic/dopaminergic subtype in the glomerular layer, no information exists concerning the generation of the other subtypes. Here we show that the recently identified zinc finger transcription factor Sp8 is expressed in neurogenic regions, which give...
The ability to remember emotional events is crucial for adapting to biologically and socially significant situations. Little is known, however, about the nature of the neural interactions supporting the integration of mnemonic and emotional information. Using fMRI and dynamic models of effective connectivity, we examined regional neural activity and specific interactions between brain regions during...
The mechanisms behind the induction of cellular correlates of memory by sensory input and their contribution to meaningful behavioral changes are largely unknown. We previously reported a graded memory in the form of sensorimotor adaptation in the electromotor output of electric fish. Here we show that the mechanism for this adaptation is a synaptically induced long-lasting shift in intrinsic neuronal...
In this issue of Neuron, Borgland et al. report that the arousal-associated peptide orexin enhances LTP-like changes in glutamatergic excitability of ventral tegmental dopamine neurons. This parallels a similar effect of corticotropin-releasing factor and suggests a form of neuroadaptation that increases the likelihood of addiction relapse.
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