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Pathological behaviors such as problem gambling or shopping are characterized by compulsive choice despite alternative options and negative costs. Reinforcement learning algorithms allow a computation of prediction error, a comparison of actual and expected outcomes, which updates our predictions and influences our subsequent choices. Using a reinforcement learning model, we show data consistent with...
Only doubling or tripling α-synuclein expression significantly increases the risk of developing Parkinson's disease. In this issue of Neuron, Nemani et al. show that this modest overexpression of α-synuclein does not lead to obvious toxicity in the near term, but impairs glutamate and dopamine release, potentially leading to broad network dysfunction and eventual pathology.
New neurons are added to the adult brain throughout life, but only half ultimately integrate into existing circuits. Sensory experience is an important regulator of the selection of new neurons but it remains unknown whether experience provides specific patterns of synaptic input or simply a minimum level of overall membrane depolarization critical for integration. To investigate this issue, we genetically...
The density of GABA A receptors (GABA A Rs) at synapses regulates brain excitability, and altered inhibition may contribute to Huntington's disease, which is caused by a polyglutamine repeat in the protein huntingtin. However, the machinery that delivers GABA A Rs to synapses is unknown. We demonstrate that GABA A Rs are trafficked to synapses by the kinesin family...
During natural vision, the entire visual field is stimulated by images rich in spatiotemporal structure. Although many visual system studies restrict stimuli to the classical receptive field (CRF), it is known that costimulation of the CRF and the surrounding nonclassical receptive field (nCRF) increases neuronal response sparseness. The cellular and network mechanisms underlying increased response...
Abnormal visual input during development has dramatic effects on the visual system. How does the adult visual system respond when input is corrected? MM lost his left eye and became blind in the right due to corneal damage at the age of 3. At age 46, MM regained his retinal image, but his visual abilities, even seven years following the surgery, remain severely limited, and he does not rely on vision...
Most depressed patients don't respond to their first drug treatment, and the reasons for this treatment resistance remain enigmatic. Human studies implicate a polymorphism in the promoter of the serotonin-1A (5-HT 1A ) receptor gene in increased susceptibility to depression and decreased treatment response. Here we develop a new strategy to manipulate 5-HT 1A autoreceptors in raphe...
Cytokines produced during infection/inflammation activate adaptive central nervous system (CNS) responses, including acute stress responses mediated by the hypothalamo-pituitary-adrenal (HPA) axis. The mechanisms by which cytokines engage HPA control circuitry remain unclear, though stimulated release of prostanoids from neighboring vascular cells has been implicated in this regard. How specific vascular...
The mechanisms underlying the brain response to systemic inflammation remain unclear. In this issue of Neuron, Serrats and colleagues demonstrate that two cell types that produce prostaglandins that act on the brain, perivascular and endothelial cells, have an unexpectedly complex interaction in regulating the timing and types of brain responses that occur.
Learned vocalizations depend on the ear's ability to monitor and ultimately instruct the voice. Where is auditory feedback processed in the brain, and how does it modify motor networks for learned vocalizations? Here we addressed these questions using singing-triggered microstimulation and chronic recording methods in the singing zebra finch, a small songbird that relies on auditory feedback to learn...
During development of the central nervous system, precise synaptic connections between presynaptic and postsynaptic neurons are formed. While significant progress has been made in our understanding of AMPA receptor trafficking during synaptic plasticity, less is known about the molecules that recruit AMPA receptors to nascent synapses during synaptogenesis. Here we identify a type II transmembrane...
One literature treats the hippocampus as a purely cognitive structure involved in memory; another treats it as a regulator of emotion whose dysfunction leads to psychopathology. We review behavioral, anatomical, and gene expression studies that together support a functional segmentation into three hippocampal compartments: dorsal, intermediate, and ventral. The dorsal hippocampus, which corresponds...
The protein α-synuclein accumulates in the brain of patients with sporadic Parkinson's disease (PD), and increased gene dosage causes a severe, dominantly inherited form of PD, but we know little about the effects of synuclein that precede degeneration. α-Synuclein localizes to the nerve terminal, but the knockout has little if any effect on synaptic transmission. In contrast, we now find that the...
In this issue of Neuron, Richardson-Jones et al. report on a novel genetic approach to conditionally and specifically dampen the function of the 5-HT 1A autoreceptor in mice to study its role on the 5-HT system and on the antidepressant-like effect of the selective serotonin reuptake inhibitor (SSRI) fluoxetine.
Hypothalamic dopamine neurons inhibit pituitary prolactin secretion. In this issue of Neuron, Lyons et al. provide evidence for a novel model, whereby the excitatory neuropeptide TRH depolarizes gap-junction-coupled dopamine neurons, leading to a shift in the population pattern of action potentials from phasic burst firing to regular tonic firing, hypothetically reducing dopamine release while increasing...
Centrosome functions are important in multiple brain developmental processes. Proper functioning of the centrosome relies on assembly of protein components into the pericentriolar material. This dynamic assembly is mediated by the trafficking of pericentriolar satellites, which are comprised of centrosomal proteins. Here we demonstrate that trafficking of pericentriolar satellites requires the interaction...
We rely on our visual system to cope with the vast barrage of incoming light patterns and to extract features from the scene that are relevant to our well-being. The necessary reduction of visual information already begins in the eye. In this review, we summarize recent progress in understanding the computations performed in the vertebrate retina and how they are implemented by the neural circuitry...
Abnormally enhanced N-methyl-D-aspartate (NMDA) receptor function is implicated in Huntington's disease (HD). In this issue of Neuron and a recent issue of Nature Medicine, an abnormal balance between the activity of NMDA receptors at synaptic (prosurvival) and extrasynaptic (proapoptotic) sites has been uncovered in a cellular and a mouse model of HD.
The superior colliculus (SC) is the first station in a subcortical relay of retinal information to extrastriate visual cortex. Ascending SC projections pass through pulvinar and LGN on their way to cortex, but it is not clear how many synapses are required to complete these circuits or which cortical areas are involved. To examine this relay directly, we injected transynaptic rabies virus into several...
The pituitary hormone, prolactin, triggers lactation in nursing mothers. Under nonlactating conditions, prolactin secretion is suppressed by powerful inhibition from hypothalamic tuberoinfundibular dopamine (TIDA) neurons. Although firing pattern has been suggested as integral to neuroendocrine control, the electrical behavior of TIDA cells remains unknown. We demonstrate that rat TIDA neurons discharge...
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