Experience-dependent formation and removal of synapses are essential throughout life. For instance, GABAergic synapses are removed to facilitate learning, and strong excitatory activity is accompanied by formation of inhibitory synapses to maintain coordination between excitation and inhibition. We recently discovered that active dendrites trigger the growth of inhibitory synapses via CB1 receptor-mediated endocannabinoid signaling, but the underlying mechanism remained unclear. Using two-photon microscopy to monitor the formation of individual inhibitory boutons in hippocampal organotypic slices from mice (both sexes), we found that CB1 receptor activation mediated the formation of inhibitory boutons and promoted their subsequent stabilization. Inhibitory bouton formation did not require neuronal activity and was independent of Gi/o protein signaling, but was directly induced by elevating cAMP levels using forskolin and by activating Gs proteins using DREADDs. Blocking PKA activity prevented CB1 receptor-...

The structural plasticity of dendritic spines is considered to be an important basis of synaptic plasticity, learning, and memory. Here, we induced input-specific structural LTP (sLTP) in single dendritic spines in organotypic hippocampal slices from mice of either sex and performed ultrastructural analyses of the spines using efficient correlative light and electron microscopy. We observed reorganization of the PSD nanostructure, such as perforation and segmentation, at 2–3, 20, and 120 min after sLTP induction. In addition, PSD and nonsynaptic axon–spine interface (nsASI) membrane expanded unevenly during sLTP. Specifically, the PSD area showed a transient increase at 2–3 min after sLTP induction. The PSD growth was to a degree less than spine volume growth at 2–3 min and 20 min after sLTP induction but became similar at 120 min. On the other hand, the nsASI area showed a profound and lasting expansion, to a degree similar to spine volume growth throughout the process. These rapid ultrastructural changes...

The mouse auditory cortex is comprised of several auditory fields spanning the dorsoventral axis of the temporal lobe. The ventral most auditory field is the temporal association cortex (TeA), which remains largely unstudied. Using Neuropixels probes, we simultaneously recorded from primary auditory cortex (AUDp), secondary auditory cortex (AUDv), and TeA, characterizing neuronal responses to pure tones and frequency modulated (FM) sweeps in awake head-restrained female mice. As compared with AUDp and AUDv, single-unit (SU) responses to pure tones in TeA were sparser, delayed, and prolonged. Responses to FMs were also sparser. Population analysis showed that the sparser responses in TeA render it less sensitive to pure tones, yet more sensitive to FMs. When characterizing responses to pure tones under anesthesia, the distinct signature of TeA was changed considerably as compared with that in awake mice, implying that responses in TeA are strongly modulated by non-feedforward connections. Together, these fi...

Anatomical organization of the primate cortex varies as a function of total brain size, where possession of a larger brain is accompanied by disproportionate expansion of associative cortices alongside a relative contraction of sensorimotor systems. However, equivalent scaling maps are not yet available for regional white matter anatomy. Here, we use three large-scale neuroimaging datasets to examine how regional white matter volume (WMV) scales with interindividual variation in brain volume among typically developing humans (combined N = 2391: 1247 females, 1144 males). We show that WMV scaling is regionally heterogeneous: larger brains have relatively greater WMV in anterior and posterior regions of cortical white matter, as well as the genu and splenium of the corpus callosum, but relatively less WMV in most subcortical regions. Furthermore, regions of positive WMV scaling tend to connect previously-defined regions of positive gray matter scaling in the cortex, revealing a coordinated coupling of region...

JNeurosci is publishing an Expression of Concern for the article, “N-Cadherin Promotes Recruitment and Migration of Neural Progenitor Cells from the SVZ Neural Stem Cell Niche into Demyelinated Lesions,” by Michael Klingener, Manideep Chavali, Jagdeep Singh, Nadia McMillan, Alexandra Coomes,

The white matter (WM) architecture of the human brain changes in response to training, though fine-grained temporal characteristics of training-induced white matter plasticity remain unexplored. We investigated white matter microstructural changes using diffusion tensor imaging at five different time points in 26 sighted female adults during 8 months of training on tactile braille reading. Our results show that training-induced white matter plasticity occurs both within and beyond the trained sensory modality, as reflected by fractional anisotropy (FA) increases in somatosensory and visual cortex, respectively. The observed changes followed distinct time courses, with gradual linear FA increase along the training in the somatosensory cortex and sudden visual cortex cross-modal plasticity occurring after braille input became linguistically meaningful. WM changes observed in these areas returned to baseline after the cessation of learning in line with the supply–demand model of plasticity. These results also...

Activity-dependent insertion of the tropomyosin-related kinase B (TrkB) receptor into the plasma membrane can explain, in part, the preferential effect of brain-derived neurotrophic factor (BDNF) on active neurons and synapses; however, the underlying molecular mechanisms remain obscure. Here, we report a novel function for carboxypeptidase E (CPE) in controlling chemical long-term potentiation stimuli-induced TrkB surface delivery in hippocampal neurons. Total internal reflection fluorescence assays and line plot assays showed that CPE facilitates TrkB transport from dendritic shafts to the plasma membrane. The Box2 domain in the juxtamembrane region of TrkB and the C terminus of CPE are critical for the activity-dependent plasma membrane insertion of TrkB. Moreover, the transactivator of transcription TAT-CPE452-466, which could block the association between CPE and TrkB, significantly inhibited neuronal activity-enhanced BDNF signaling and dendritic spine morphologic plasticity in cultured hippocampal n...

Radial glial progenitor cells (RGCs) in the dorsal telencephalon directly or indirectly produce excitatory projection neurons and macroglia of the neocortex. Recent evidence shows that the pool of RGCs is more heterogeneous than originally thought and that progenitor subpopulations can generate particular neuronal cell types. Using single-cell RNA sequencing, we have studied gene expression patterns of RGCs with different neurogenic behavior at early stages of cortical development. At this early age, some RGCs rapidly produce postmitotic neurons, whereas others self-renew and undergo neurogenic divisions at a later age. We have identified candidate genes that are differentially expressed among these early RGC subpopulations, including the transcription factor Sox9. Using in utero electroporation in embryonic mice of either sex, we demonstrate that elevated Sox9 expression in progenitors affects RGC cell cycle duration and leads to the generation of upper layer cortical neurons. Our data thus reveal molecul...

The G-protein-gated inwardly rectifying potassium (Kir3/GIRK) channel is the effector of many G-protein-coupled receptors (GPCRs). Its dysfunction has been linked to the pathophysiology of Down syndrome, Alzheimer's and Parkinson's diseases, psychiatric disorders, epilepsy, drug addiction, or alcoholism. In the hippocampus, GIRK channels decrease excitability of the cells and contribute to resting membrane potential and inhibitory neurotransmission. Here, to elucidate the role of GIRK channels activity in the maintenance of hippocampal-dependent cognitive functions, their involvement in controlling neuronal excitability at different levels of complexity was examined in C57BL/6 male mice. For that purpose, GIRK activity in the dorsal hippocampus CA3−CA1 synapse was pharmacologically modulated by two drugs: ML297, a GIRK channel opener, and Tertiapin-Q (TQ), a GIRK channel blocker. Ex vivo , using dorsal hippocampal slices, we studied the effect of pharmacological GIRK modulation on synaptic plasticity proce...