Endocannabinoid Signaling Contributes to Experience-Induced Increase of Synaptic Release Sites From Parvalbumin Interneurons in Mouse Visual Cortex

Abstract

During postnatal development of the visual cortex between eye-opening to puberty, visual experience promotes a gradual increase in the strength of inhibitory synaptic connections from parvalbumin-positive interneurons (PV-INs) onto layer 2/3 pyramidal cells. However, the detailed connectivity properties and molecular mechanisms underlying these developmental changes are not well understood. Using dual-patch clamp in brain slices from G42 mice, we revealed that both connection probability and the number of synaptic release sites contributed to the enhancement of synaptic strength. The increase of release site number was hindered by dark rearing from eye-opening and rescued by 3-days re-exposure to the normal visual environment. The effect of light re-exposure on restoring synaptic release sites in dark reared mice was mimicked by the agonist of cannabinoid-1 (CB1) receptors and blocked by an antagonist of these receptors, suggesting a role for endocannabinoid signaling in lightinduced maturation of inhibitory connectivity from PV-INs to pyramidal cells during postnatal development.

Astrocyte CB1 receptors are required for inhibitory maturation and ocular dominance plasticity in the mouse visual cortex

“…CB1Rs are traditionally thought to reside on presynaptic axon terminals. However, the parvalbumin-expressing fastspiking interneurons that undergo developmental maturation 5,10 are thought to express no or only low levels of CB1Rs [11][12][13] . Furthermore, it was previously shown that astrocytes also express CB1Rs 6,7 , which are involved in plasticity of developing sensory circuits 7 .…”

“…In addition to the general increase in synaptic strength, synaptic release and short-term depression decrease with development, resulting in more reliable and precise inhibition [23][24][25] . At inhibitory synapses formed by parvalbumin-expressing fast-spiking interneurons the maturation of inhibitory synaptic strength and dynamics depends on CB1R signaling, since both processes are blocked by CB1R antagonist treatment or by genetic CB1R knockout 4,5,10 . This has been puzzling, since parvalbumin-expressing interneurons express no or only low levels of CB1Rs [11][12][13] .…”

Endocannabinoids and cortical plasticity: CB1R as a possible regulator of the excitation/inhibition balance in health and disease

“…This is further confirmed by the visual cortex transcriptomics data set from the Allen brain institute (Allen Institute for Brain Science, 2018). Even if PV is not part of this list of cell markers, PV + interneurons have been shown to be sensitive to CB1R ligands (Jiang et al., 2010) and the experience‐induced maturation of their inhibitory synapses appears regulated by CB1R ligands (Huang & Kirkwood, 2020). With CB1R on many different interneuron classes, indirect modulation of PV + interneurons, by disinhibition, for example is a highly likely possibility.…”

Prenatal alcohol and cannabis exposure can have opposing and region‐specific effects on parvalbumin interneuron numbers in the hippocampus

“…While no completely parallel literature was identified, Vargish et al found a decrease in the number of cholecystokinin-positive positive interneurons in theDG,however,onlyinthosederivedfromthecaudalganglionic eminence(Vargish et al, 2017). It is important to note that while cholecystokinin-positiveandPVinterneuronsarefoundinthehippocampus,mostcannabinoidreceptor1(CB1)receptorsarefound on cholecystokinin-positive positive interneurons and not PVpositiveinterneurons(deSalas-Quirogaetal.,2020),althoughthere is evidence of this outside the hippocampus(Huang & Kirkwood, 2020). This is relevant because THC acts predominantly on CB1 receptors; thus, it isexpectedthat THCwould affect PVand CCK interneurons differently.…”