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Review
, 41 (5), 373-380

Molecular Mechanisms of Synaptic Specificity: Spotlight on Hippocampal and Cerebellar Synapse Organizers

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Review

Molecular Mechanisms of Synaptic Specificity: Spotlight on Hippocampal and Cerebellar Synapse Organizers

Dongseok Park et al. Mol Cells.

Abstract

Synapses and neural circuits form with exquisite specificity during brain development to allow the precise and appropriate flow of neural information. Although this property of synapses and neural circuits has been extensively investigated for more than a century, molecular mechanisms underlying this property are only recently being unveiled. Recent studies highlight several classes of cell-surface proteins as organizing hubs in building structural and functional architectures of specific synapses and neural circuits. In the present mini-review, we discuss recent findings on various synapse organizers that confer the distinct properties of specific synapse types and neural circuit architectures in mammalian brains, with a particular focus on the hippocampus and cerebellum.

Keywords: brain disorder; neural circuit; specificity; synapse; synaptic adhesion.

Figures

Fig. 1
Fig. 1. Overview of the basic neural circuit architectures of the hippocampus and cerebellum
(A) Illustration of the hippocampal circuitry. The canonical projections involving entorhinal cortical neurons and various hippocampal neurons are depicted by solid arrows. Abbreviations: DG, dentate gyrus; LEC, lateral entorhinal cortex; MEC, medial entorhinal cortex; and SUB, subiculum. (B) Illustration of the cerebellar circuitry. The canonical projections involving various cerebellar neurons are depicted by solid arrows. Abbreviations: CF, climbing fiber; and PF, parallel fiber.
Fig. 2
Fig. 2. Key molecular determinants that regulate specific properties of hippocampal and cerebellar neural circuits
(A) Simplified neural circuit schematic showing projections from the entorhinal cortex (EC) to the hippocampal CA1 subfield (red), from the hippocampal CA3 subfield to the CA1 subfield (blue), from the hippocampal CA1 pyramidal neuron to somatostatin-positive inhibitory neuron (purple). A subset of the indicated cell-surface proteins confers the synaptic specificity between hippocampal CA1 pyramidal neurons and other brain area neurons; (a) connections of the CA3 with distal dendrites of hippocampal CA1 in the SO layer; (b) connections of somatostatin (SOM)-positive interneurons with hippocampal CA1 in the SO layer; and (c) connections of the EC with hippocampal CA1 in the SLM layer. Abbreviations: AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; CDH, cadherin: EC, entorhinal cortex; Elfn, extracellular leucine-rich repeat and fibronectin type III domain containing; Lphn, latrophilin; mGluR, metabotropic glutamate receptor; NGL, netrin G-ligand; NL, neuroligin; Nrxn, neurexin; S.L.M., stratum lacunosum moleculare; S.O., stratum oriens; SOM, somatostatin; S.R., stratum radiatum; and PV, parvalbumin. (B) Simplified schematic highlighting the diversity of molecular players that confer synaptic specificity in cerebellar neural circuits. Abbreviations: AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; BC, basket cell; BAI, brain-specific angiogenesis inhibitor; Cbln, cerebellin precursor; C1ql, complement component 1 (q subcomponent-like); CF, climbing fiber; GABA, γ-aminobutyric acid; GABAR, GABA-type ionotropic receptor; GC, granule cell; Glu, glutamate; GluD, glutamate receptor δ family; MF, mossy fiber; NMDAR, N-methyl-D-aspartate receptor; Nrxn, neurexin; NL, neuroligin; PC, purkinje cell; PF, parallel fiber; and SC, stellate cell.

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