Deletion of the cannabinoid CB₁ receptor impacts on the ultrastructure of the cerebellar parallel fiber‐Purkinje cell synapses

Abstract

The cannabinoid CB 1 receptor localizes to the glutamatergic parallel fiber (PF) terminals of the cerebellar granule cells and participates in synaptic plasticity, motor control and learning that are impaired in CB 1 receptor knockout (CB 1 -KO) mice. However, whether ultrastructural changes at the PF-Purkinje cell (PC) synapses occur in CB 1 -KO remains unknown. We studied this in the vermis of the spinocerebellar lobule V and the vestibulocerebellar lobule X of CB 1 -KO and wild-type (CB 1 -WT) mice by electron microscopy. Lobule V, but not lobule X, of CB 1 -KO had significantly less and longer synapses than in CB 1 -WT. PF terminals were significantly larger in both lobules of CB 1 -KO with no changes in PC dendritic spines. The PF terminals in lobule V of CB 1 -KO contained less synaptic vesicles and lower vesicle density; by contrast, vesicle density in lobule X of CB 1 -KO remained unchangeable relative to CB 1 -WT. There were as many vesicles in lobule V of CB 1 -KO as in CB 1 -WT, but their distribution decreased drastically at 300 nm of the active zone. In lobule X of CB 1 -KO, less vesicles were found within 150 nm from the presynaptic membrane; however, no vesicles were at 450-600 nm of the active zone. A significant higher amount of synaptic vesicles close to the active zone in lobule V and X of CB 1 -KO was observed. In conclusion, the absence of CB 1 receptors strikingly and distinctively impacts on the ultrastructural architecture of the PF-PC synapses located in cerebellar lobules that differ in vulnerability to damage and motor functions.

Neuronal and synaptic morphological alterations in the hippocampus of cannabinoid receptor type 1 knockout mice

“…show that cerebellar lobules of CB1R −/− mice contain greater length of synapsis and lower vesicle density, representing ultrastructural adaptations in the absence of CB1R (Buceta et al, 2019). However, in the present work, the number of synaptic vesicles detected by electron microscopy did not show differences between CB1R −/− and CB1R +/+ .…”

“…The implication of CB1R in the synaptic structure has also been reported in the work of Tagliaferro et al (2006), which shows an increase in the number of vesicles as a result of treatment with a cannabinoid agonist and hence supports the hypothesis of a direct effect of cannabinoids on synaptic stability (Karanian, Brown, Makriyannis, Kosten, & Bahr, 2005). More recently, Buceta et al show that cerebellar lobules of CB1R −/− mice contain greater length of synapsis and lower vesicle density, representing ultrastructural adaptations in the absence of CB1R (Buceta et al, 2019). However, in the present work, the number of synaptic vesicles detected by electron microscopy did not show differences between CB1R −/− and CB1R +/+ .…”

Omega-3 Recovers Cannabinoid 1 Receptor Expression in the Adult Mouse Brain after Adolescent Binge Drinking

“…Furthermore, the M2 and Cb, both affected by EtOH, are brain regions involved in motor coordination [46,47] and EtOH intake leads to motor incoor-dination and ataxia [43]. Our present results show a significant decrease in CB 1 staining in the cerebellar molecular layer, where the receptor is mostly localized to the excitatory granule cell parallel fiber terminals [48]. However, the lack of CB 1 receptors does not seem to cause evident cerebellar motor deficits [49], despite their role in motor learning [50].…”

Influence of prenatal cannabinoid exposure on early development and beyond

“…Moreover, genetic deletion of CB1 in preclinical models is associated with altered morphology or function in numerous brain structures. These include cerebellum ( 36 ), cortex ( 37 – 39 ), striatum ( 40 ), bed nucleus of the stria terminalis ( 41 ), and other mesocorticolimbic areas ( 42 ).…”