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The circuitry of the striatum is characterized by two organizational plans: the division into striosome and matrix compartments, thought to mediate evaluation and action, and the direct and indirect pathways, thought to promote or suppress behavior. The developmental origins of these organizations and their developmental relationships are unknown, leaving a conceptual gap in understanding the cortico-basal...
Inhibitory interneurons participate in mnemonic processes. However, defined roles for identified interneuron populations are scarce. A subpopulation of oriens lacunosum-moleculare (OLM) interneurons genetically defined by the expression of the nicotinic receptor α2 subunit has been shown to gate information carried by either the temporoammonic pathway or Schaffer collaterals in vitro. Here we set...
N6-methyladenosine (m6A) and N6,2′-O-dimethyladenosine (m6Am) are abundant mRNA modifications that regulate transcript processing and translation. The role of both, here termed m6A/m, in the stress response in the adult brain in vivo is currently unknown. Here, we provide a detailed analysis of the stress epitranscriptome using m6A/m-seq, global and gene-specific m6A/m measurements. We show that stress...
NMDA-type glutamate receptors (NMDARs) are ligand-gated ion channels that mediate excitatory neurotransmission in the CNS. Here we describe functional and single-channel properties of triheteromeric GluN1/GluN2A/GluN2C receptors, which contain two GluN1, one GluN2A, and one GluN2C subunits. This NMDAR has three conductance levels and opens in bursts similar to GluN1/GluN2A receptors but with a single-channel...
How presynaptic inputs and neurotransmitter release dynamics are distributed along a dendritic tree is not well established. Here, we show that presynaptic boutons that form onto basal dendrites of CA1 pyramidal neurons display a decrease in active zone (AZ) size with distance from the soma, resulting in a distance-dependent increase in short-term facilitation. Our findings suggest that the spatial...
Social communication has traditionally been studied from the point of view of an isolated spectator not participating in social interaction. In this issue of Neuron, using advanced functional imaging, Shepherd and Freiwald (2018) explore the functional neuroanatomy of social communication in the brain of socially interacting nonhuman primates and discover three large-scale brain networks dedicated...
Looming visual stimuli result in escape responses that are conserved from insects to humans. Despite their importance for survival, the circuits mediating visual startle have only recently been explored in vertebrates. Here we show that the zebrafish thalamus is a luminance detector critical to visual escape. Thalamic projection neurons deliver dim-specific information to the optic tectum, and ablations...
Congenital hydrocephalus (CH), featuring markedly enlarged brain ventricles, is thought to arise from failed cerebrospinal fluid (CSF) homeostasis and is treated with lifelong surgical CSF shunting with substantial morbidity. CH pathogenesis is poorly understood. Exome sequencing of 125 CH trios and 52 additional probands identified three genes with significant burden of rare damaging de novo or transmitted...
We reveal a central role for chance neuronal events in the decision of a male fly to court, which can be modeled as a coin flip with odds set by motivational state. The decision is prompted by a tap of a female with the male’s pheromone-receptor-containing foreleg. Each tap evokes competing excitation and inhibition onto P1 courtship command neurons. A motivating dopamine signal desensitizes P1 to...
Cerebral blood flow increases in regions of increased brain activity. In this issue of Neuron, Rungta et al. (2018) characterize the contribution of different vascular compartments in generating this increase and outline the time course of arteriole and capillary dilation in generating functional hyperemia.
A genetic informed approach sheds new light on the biology of congenital hydrocephalus (CH), on which previous knowledge of the genetic background is scanty. In this issue, Furey et al. (2018) discover that variants in four genes associated with neurogenesis are implicated in CH.
In an interview with Neuron, Kelsey Martin shares how volunteering with the Peace Corps motivated her to become a scientist and how reductionists science has fueled her work on understanding how experience changes brain connectivity. She also shares her hope for more synergy between the clinical and basic neurosciences.
Functional hyperemia, a regional increase of blood flow triggered by local neural activation, is used to map brain activity in health and disease. However, the spatial-temporal dynamics of functional hyperemia remain unclear. Two-photon imaging of the entire vascular arbor in NG2-creERT2;GCaMP6f mice shows that local synaptic activation, measured via oligodendrocyte precursor cell (OPC) Ca2+ signaling,...
All primates communicate. To dissect the neural circuits of social communication, we used fMRI to map non-human primate brain regions for social perception, second-person (interactive) social cognition, and orofacial movement generation. Face perception, second-person cognition, and face motor networks were largely non-overlapping and acted as distinct functional units rather than an integrated feedforward-processing...
Pyramidal neurons express rich repertoires of leucine-rich repeat (LRR)-containing adhesion molecules with similar synaptogenic activity in culture. The in vivo relevance of this molecular diversity is unclear. We show that hippocampal CA1 pyramidal neurons express multiple synaptogenic LRR proteins that differentially distribute to the major excitatory inputs on their apical dendrites. At Schaffer...
Human neuroimaging research has transitioned from mapping local effects to developing predictive models of mental events that integrate information distributed across multiple brain systems. Here we review work demonstrating how multivariate predictive models have been utilized to provide quantitative, falsifiable predictions; establish mappings between brain and mind with larger effects than traditional...
Epitranscriptomic modification of mRNA affects its metabolism and has recently been shown to regulate brain development. Two studies in this issue of Neuron, Koranda et al. (2018) and Engel et al. (2018), uncover dynamic and critical roles of m6A/m RNA modifications in the adult mammalian brain in regulating physiological and stress-induced behaviors.
N6-methyladenosine (m6A) regulates mRNA metabolism and translation, serving as an important source of post-transcriptional regulation. To date, the functional consequences of m6A deficiency within the adult brain have not been determined. To achieve m6A deficiency, we deleted Mettl14, an essential component of the m6A methyltransferase complex, in two related yet discrete mouse neuronal populations:...
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