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Mammalian cortex features a vast diversity of neuronal cell types, each with characteristic anatomical, molecular and functional properties. Synaptic connectivity powerfully shapes how each cell type participates in the cortical circuit, but mapping connectivity rules at the resolution of distinct cell types remains difficult. Here, we used millimeter-scale volumetric electron microscopy1to investigate the connectivity of all inhibitory neurons across a densely-segmented neuronal population of 1352 cells spanning all layers of mouse visual cortex, producing a wiring diagram of inhibitory connections with more than 70,000 synapses. Taking a data-driven approach inspired by classical neuroanatomy, we classified inhibitory neurons based on the relative targeting of dendritic compartments and other inhibitory cells and developed a novel classification of excitatory neurons based on the morphological and synaptic input properties. The synaptic connectivity between inhibitory cells revealed a novel class of disinhibitory specialist targeting basket cells, in addition to familiar subclasses. Analysis of the inhibitory connectivity onto excitatory neurons found widespread specificity, with many interneurons exhibiting differential targeting of certain subpopulations spatially intermingled with other potential targets. Inhibitory targeting was organized into “motif groups,” diverse sets of cells that collectively target both perisomatic and dendritic compartments of the same excitatory targets. Collectively, our analysis identified new organizing principles for cortical inhibition and will serve as a foundation for linking modern multimodal neuronal atlases with the cortical wiring diagram.
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Neurotransmission and neuromodulation systems in the learning and memory network of Octopus vulgaris
The vertical lobe (VL) in the octopus brain plays an essential role in its sophisticated learning and memory. Early anatomical studies suggested that the VL is organized in a “fan-out fan-in” connectivity matrix comprising only three morphologically identified neuron types; input axons from the superior frontal lobe (SFL) innervating en passant millions of small amacrine interneurons (AMs) which converge sharply onto large VL output neurons (LNs). Recent physiological studies confirmed the feedforward excitatory connectivity: a glutamatergic synapse at the first SFL-to-AM synaptic layer and a cholinergic AM-to-LNs synapse. SFL-to-AMs synapses show a robust hippocampal-like activity-dependent long-term potentiation (LTP) of transmitter release. 5-HT, octopamine, dopamine, and nitric oxide modulate short- and long-term VL synaptic plasticity. Here we present a comprehensive histolabeling study to better characterize the neural elements in the VL. We generally confirmed glutamatergic SFLs and cholinergic AMs. Intense labeling for NOS activity in the AMs neurites fitted with the NO-dependent presynaptic LTP mechanism at the SFL-to-AM synapse. New discoveries here reveal more heterogeneity of the VL neurons than previously thought. GABAergic AMs suggest a subpopulation of inhibitory interneurons in the first input layer. Clear GABA labeling in the cell bodies of LNs supported an inhibitory VL output yet the LNs co-expressed FMRFamide-like neuropeptides suggesting an additional neuromodulatory role of the VL output. Furthermore, a group of LNs was glutamatergic. A new cluster of cells organized in a “deep nucleus” showed rich catecholaminergic labeling and may play a role in intrinsic neuromodulation. In situ hybridization and immunolabeling allowed characterization and localization of a rich array of neuropeptides and neuromodulators, likely involved in reward/punishment signals. This analysis of the fast transmission system, together with the newly found cellular elements helps integrate behavioral, physiological, pharmacological, and connectome findings into a more comprehensive understanding of an efficient learning and memory network.
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- Award ID(s):
- 1645219
- PAR ID:
- 10312816
- Date Published:
- Journal Name:
- bioRxiv
- ISSN:
- 2692-8205
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1002/jmor.21459
