In:
Science, American Association for the Advancement of Science (AAAS), Vol. 375, No. 6586 ( 2022-03-18)
Kurzfassung:
Synaptic plasticity, the process by which neurons adjust the strengths of their thousands of inputs, allows animals to adapt to their environment. Decades of research have established Ca 2+ as a central mediator of synaptic plasticity. Historically, most investigations into the role of Ca 2+ in plasticity have focused on its influx through voltage-gated channels that open when synaptic input depolarizes a neuron. However, a large body of in vitro research suggests that an alternate source of Ca 2+ may also play a potent role in shaping plasticity: the endoplasmic reticulum (ER). The ER stores Ca 2+ in vast quantities within a cell and can release this store in response to strong synaptic input through intracellular Ca 2+ release (ICR). The ER is therefore poised to shape the magnitude and spatial distribution of Ca 2+ during plasticity induction. Despite its potential role in synaptic plasticity, ICR has never been investigated in mammalian neurons in vivo. RATIONALE To test whether ICR participates in experience-dependent plasticity, we focused on pyramidal neurons of hippocampal area CA1 (CA1PNs). CA1PNs receive excitatory inputs from multiple afferent circuits, carrying complementary streams of information about an animal’s environment that impinge onto distinct compartments of the CA1PN dendritic arbor. As an animal explores a new environment, CA1PNs integrate these inputs to form spatially tuned receptive fields known as place fields that manifest as a neuron firing when an animal occupies a particular location. Recent work has characterized an in vivo plasticity mechanism driving place field formation: behavioral time-scale plasticity (BTSP). BTSP is initiated by a large, prolonged dendritic depolarization (plateau potential) that ultimately potentiates synaptic inputs received during a seconds-long time window corresponding to the time of plateau onset. Here, we used CA1PNs and BTSP as a model system to test whether ICR participates in the experience-dependent emergence of feature selectivity. We implemented a series of tools based on single-cell electroporation allowing us to (i) manipulate the cytosolic impact of ICR at single-cell resolution using conditional gene deletion, (ii) optogenetically induce place cells, and (iii) image somatic and dendritic Ca 2+ dynamics simultaneously during spatial navigation. RESULTS The gene Pdzd8 encodes a recently identified ER-mitochondrial tethering protein that, when deleted, leads to unrestricted ICR. We found that Pdzd8 deletion in single adult CA1PNs in vivo substantially increased the level of spatial co-tuning observed in their apical dendrites relative to the soma of CA1 place cells, a phenomenon not observed in basal dendrites, which were already highly co-tuned with the soma in control CA1PNs. Maximizing ICR leads to more-stable retention of place cell spatial tuning over time and alters the integrative properties of their apical dendrites to shape output-level receptive fields. CONCLUSION ICR plays a key and previously uncharacterized role in shaping the dendritic integration properties of CA1PNs during the emergence of feature selectivity. Therefore, ICR cooperates with circuit-level architecture in vivo to promote the emergence of behaviorally relevant forms of plasticity in a compartment-specific manner. ICR shapes receptive fields important for spatial navigation. We tested the role of ICR in neuronal feature selectivity by genetically ablating contact sites between ER and mitochondria (Mito) in single pyramidal neurons of hippocampal area CA1 in vivo. Increasing the impact of ICR on cytoplasmic Ca 2+ altered integrative properties in apical dendrites, widening and stabilizing “place fields” over time. Illustration by Matteo Farinella
Materialart:
Online-Ressource
ISSN:
0036-8075
,
1095-9203
DOI:
10.1126/science.abm1670
Sprache:
Englisch
Verlag:
American Association for the Advancement of Science (AAAS)
Publikationsdatum:
2022
ZDB Id:
128410-1
ZDB Id:
2066996-3
ZDB Id:
2060783-0
SSG:
11
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