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Larry Abbott worked in theoretical physics before switching to theoretical neuroscience. In an interview with Neuron, he talks about his current interests, highlights recent developments in the acquisition of large amounts of neural activity data, and discusses the challenges associated with providing a cohesive understanding of the brain.
Alzheimer’s disease (AD) is characterized by cognitive decline and neuronal network dysfunction, but the underlying mechanisms remain unknown. In the hippocampus, microcircuit activity during learning and memory processes is tightly controlled by O-LM interneurons. Here, we investigated the effect of beta-amyloidosis on O-LM interneuron structural and functional connectivity, combining two-photon...
Adolescence is a time of tumultuous behavior that may result, in part, from brain circuitry that enhances reward seeking. In this issue of Neuron, Davidow et al. (2016) present a convincing argument that adolescent brain functionality can be adaptive in certain contexts, particularly probabilistic learning environments.
An influential striatal model postulates that neural activities in the striatal direct and indirect pathways promote and inhibit movement, respectively. Normal behavior requires coordinated activity in the direct pathway to facilitate intended locomotion and indirect pathway to inhibit unwanted locomotion. In this striatal model, neuronal population activity is assumed to encode locomotion relevant...
Neocortical excitatory and inhibitory neurons derive from distinct progenitor domains during embryonic development and migrate to their final positions, where they assemble into functional circuits. This process appears to be influenced by lineage relationships among locally born excitatory neurons, raising the intriguing possibility that this might be true for cortical interneurons. Two recent articles...
In this issue of Neuron, Tochitsky et al. (2016) have identified the mechanism by which small-molecule photoswitches enter and specifically activate retinal OFF-ganglion cells in degenerated retinas. This drug development is a tremendous step toward the treatment of blindness, regardless of the underlying mutation.
Progress in clinical and affective neuroscience is redefining psychiatric illness as symptomatic expression of cellular/molecular dysfunctions in specific brain circuits. Post-traumatic stress disorder (PTSD) has been an exemplar of this progress, with improved understanding of neurobiological systems subserving fear learning, salience detection, and emotion regulation explaining much of its phenomenology...
This Matters Arising Response paper addresses the Sultan et al. (2016) Matters Arising paper, published concurrently in Neuron. Clonally related excitatory neurons maintain a coherent relationship following their specification and migration. Whether cortical interneurons behave similarly is a fundamental question in developmental neuroscience. In Mayer et al. (2015), we reported that sibling interneurons...
Mike Greenberg is a visionary leader with a passion for his scientific endeavors and training the next generation of neuroscientists. In an interview with Neuron, he discusses the inspiration he finds from the past, the challenges and promises for the field, and how his independent streak and love of discovery fuels him.
Adolescents are notorious for engaging in reward-seeking behaviors, a tendency attributed to heightened activity in the brain’s reward systems during adolescence. It has been suggested that reward sensitivity in adolescence might be adaptive, but evidence of an adaptive role has been scarce. Using a probabilistic reinforcement learning task combined with reinforcement learning models and fMRI, we...
Precise connection of thalamic barreloids with their corresponding cortical barrels is critical for processing of vibrissal sensory information. Here, we show that PRG-2, a phospholipid-interacting molecule, is important for thalamocortical axon guidance. Developing thalamocortical fibers both in PRG-2 full knockout (KO) and in thalamus-specific KO mice prematurely entered the cortical plate, eventually...
For reliable stimulus identification, sensory codes have to be robust by including redundancy to combat noise, but redundancy sacrifices coding efficiency. To address how experience affects the balance between the robustness and efficiency of sensory codes, we probed odor representations in the mouse olfactory bulb during learning over a week, using longitudinal two-photon calcium imaging. When mice...
Azobenzene photoswitches confer light sensitivity onto retinal ganglion cells (RGCs) in blind mice, making these compounds promising candidates as vision-restoring drugs in humans with degenerative blindness. Remarkably, photosensitization manifests only in animals with photoreceptor degeneration and is absent from those with intact rods and cones. Here we show that P2X receptors mediate the entry...
Protein phosphorylation is an essential step for the expression of long-term potentiation (LTP), a long-lasting, activity-dependent strengthening of synaptic transmission widely regarded as a cellular mechanism underlying learning and memory. At the core of LTP is the synaptic insertion of AMPA receptors (AMPARs) triggered by the NMDA receptor-dependent activation of Ca2+/calmodulin-dependent protein...
Elucidating the transcriptional circuitry controlling forebrain development requires an understanding of enhancer activity and regulation. We generated stable transgenic mouse lines that express CreERT2 and GFP from ten different enhancer elements with activity in distinct domains within the embryonic basal ganglia. We used these unique tools to generate a comprehensive regional fate map of the mouse...
The striatum, the entry nucleus of the basal ganglia, lacks laminar or columnar organization of its principal cells; nevertheless, functional data suggest that it is spatially organized. Here we examine whether the connectivity and synaptic organization of striatal GABAergic interneurons contributes to such spatial organization. Focusing on the two main classes of striatal GABAergic interneurons (fast-spiking...
Cognition requires the dynamic modulation of effective connectivity, i.e., the modulation of the postsynaptic neuronal response to a given input. If postsynaptic neurons are rhythmically active, this might entail rhythmic gain modulation, such that inputs synchronized to phases of high gain benefit from enhanced effective connectivity. We show that visually induced gamma-band activity in awake macaque...
Addiction is a disorder of behavioral symptoms including enhanced incentive salience of drug-associated cues, but also a negative affective state. Cocaine-evoked synaptic plasticity in the reward system, particularly the nucleus accumbens (NAc), drives drug-adaptive behavior. However, how information is integrated downstream of the NAc remains unclear. Here, we identify the ventral pallidum (VP) as...
Experience alters cortical networks through neural plasticity mechanisms. During a developmental critical period, the most dramatic consequence of occluding vision through one eye (monocular deprivation) is a rapid loss of excitatory synaptic inputs to parvalbumin-expressing (PV) inhibitory neurons in visual cortex. Subsequent cortical disinhibition by reduced PV cell activity allows for excitatory...
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