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In this issue of Neuron, Threlfell et al. (2012) report that synchronous activation of cholinergic interneurons evokes striatal dopamine release by activating presynaptic nicotinic acetylcholine receptors. These findings call for a fundamental reevaluation of the long-standing view that dopamine and acetylcholine “feud” over control of striatal circuitry.
Memory and perception have long been considered separate cognitive processes, and amnesia resulting from medial temporal lobe (MTL) damage is thought to reflect damage to a dedicated memory system. Recent work has questioned these views, suggesting that amnesia can result from impoverished perceptual representations in the MTL, causing an increased susceptibility to interference. Using a perceptual...
Neurotransmitters are released by synaptic vesicle exocytosis at the active zone of a presynaptic nerve terminal. In this review, I discuss the molecular composition and function of the active zone. Active zones are composed of an evolutionarily conserved protein complex containing as core constituents RIM, Munc13, RIM-BP, α-liprin, and ELKS proteins. This complex docks and primes synaptic vesicles...
Medial temporal lobe (MTL) structures may constitute a representational hierarchy, rather than a dedicated system for memory. Barense et al. (2012) show that intact memory for object features can interfere with perception of complex objects in individuals with MTL amnesia.
We used affinity-purification mass spectrometry to identify 747 candidate proteins that are complexed with Huntingtin (Htt) in distinct brain regions and ages in Huntington's disease (HD) and wild-type mouse brains. To gain a systems-level view of the Htt interactome, we applied Weighted Correlation Network Analysis to the entire proteomic data set to unveil a verifiable rank of Htt-correlated proteins...
The molecular mechanisms that instruct the formation of synaptic layers are only incompletely understood. In this issue of Neuron, Timofeev et al. (2012) describe an instructive role for the guidance molecule Netrin and its receptor Frazzled in mediating layer-specific targeting of one photoreceptor cell type in the Drosophila visual system.
Striatal dopamine plays key roles in our normal and pathological goal-directed actions. To understand dopamine function, much attention has focused on how midbrain dopamine neurons modulate their firing patterns. However, we identify a presynaptic mechanism that triggers dopamine release directly, bypassing activity in dopamine neurons. We paired electrophysiological recordings of striatal channelrhodopsin2-expressing...
Age-related macular degeneration (AMD), a progressive condition that is untreatable in up to 90% of patients, is a leading cause of blindness in the elderly worldwide. The two forms of AMD, wet and dry, are classified based on the presence or absence of blood vessels that have disruptively invaded the retina, respectively. A detailed understanding of the molecular mechanisms underlying wet AMD has...
Neuromuscular junction (NMJ) formation requires precise interaction between motoneurons and muscle fibers. LRP4 is a receptor of agrin that is thought to act in cis to stimulate MuSK in muscle fibers for postsynaptic differentiation. Here we dissected the roles of LRP4 in muscle fibers and motoneurons in NMJ formation by cell-specific mutation. Studies of muscle-specific mutants suggest that LRP4...
Small-conductance Ca2+-activated K+ channels (SK channels) modulate excitability and curtail excitatory postsynaptic potentials (EPSPs) in neuronal dendrites. Here, we demonstrate long-lasting plasticity of intrinsic excitability (IE) in dendrites that results from changes in the gain of this regulatory mechanism. Using dendritic patch-clamp recordings from rat cerebellar Purkinje cells, we find that...
Neurons in rodent visual cortex are organized in a salt-and-pepper fashion for orientation selectivity, but it is still unknown how this functional architecture develops. A recent study reported that the progeny of single cortical progenitor cells are preferentially connected in the postnatal cortex. If these neurons acquire similar selectivity through their connections, a salt-and-pepper organization...
A shared feature of many neural circuits is their organization into synaptic layers. However, the mechanisms that direct neurites to distinct layers remain poorly understood. We identified a central role for Netrins and their receptor Frazzled in mediating layer-specific axon targeting in the Drosophila visual system. Frazzled is expressed and cell autonomously required in R8 photoreceptors for directing...
Memory enables flexible use of past experience to inform new behaviors. Although leading theories hypothesize that this fundamental flexibility results from the formation of integrated memory networks relating multiple experiences, the neural mechanisms that support memory integration are not well understood. Here, we demonstrate that retrieval-mediated learning, whereby prior event details are reinstated...
Emotional memories can persist for a lifetime but can also undergo extinction. Although we know about the mechanisms involved in expression and extinction, we know very little about the mechanisms that determine whether a specific memory would persist or not. Here, we use partial reinforcement extinction effect (PREE) to explore the neural mechanisms that differentiate persistent from labile memories...
Our visual system segments images into objects and background. Figure-ground segregation relies on the detection of feature discontinuities that signal boundaries between the figures and the background and on a complementary region-filling process that groups together image regions with similar features. The neuronal mechanisms for these processes are not well understood and it is unknown how they...
Human altruism shaped our evolutionary history and pervades social and political life. There are, however, enormous individual differences in altruism. Some people are almost completely selfish, while others display strong altruism, and the factors behind this heterogeneity are only poorly understood. We examine the neuroanatomical basis of these differences with voxel-based morphometry and show that...
Several models of associative learning predict that stimulus processing changes during association formation. How associative learning reconfigures neural circuits in primary sensory cortex to “learn” associative attributes of a stimulus remains unknown. Using 2-photon in vivo calcium imaging to measure responses of networks of neurons in primary somatosensory cortex, we discovered that associative...
Two recent papers, Li et al. (2012) in Nature and Ohtsuki et al. (2012) in this issue of Neuron, show that lineage relationships between cortical neurons impact the development of specific connectivity and functional properties of cortical circuits. However, several differences between their results highlight important questions for future investigation.
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