4.1 The wide distribution of CB1Rs across the central auditory
system
The ECS and its components have been the subject of extensive research,
particularly for their roles in synaptic plasticity and neurodevelopment
(Tzounopoulos et al., 2007; Clarke et al., 2021). While much has been
studied about the ECS and its components, particularly CB1Rs, in various
regions of the CNS, much less attention has been given to how CB1Rs are
distributed and function in the central auditory system. Cnr1
transcripts that encode CB1Rs have been detected in various brain
regions using RNA scope or in situ hybridization, however, the actual
expression characteristics of CB1Rs proteins themselves-especially in
the central auditory system-remain an underexplored area (Erben and
Buonanno, 2019; Tao et al., 2020).
In the current study, we systematically evaluated the differentiated
expression patterns of CB1Rs in the central auditory system using
immunostaining. Immunostaining is an excellent way to complement in situ
hybridization of mRNA transcripts, and allows for direct visualization
of CB1Rs proteins in specific neuronal populations and subcellular
compartments, providing valuable insights into how CB1Rs are distributed
across various auditory nuclei. Our findings demonstrated that the
expression of CB1Rs in the CN, SOC, IC, LL, MGB, and AC of mice are in
line with previous studies, further supporting the idea that CB1Rs are
widely distributed across regions of the central auditory system (Zheng
et al., 2007; Zhao et al., 2011; Ji et al., 2017). Specifically, the
observation that CB1Rs are particularly abundantly enriched in the CN,
SOC suggest that CB1Rs play a role in modulating early auditory
processing.
We also found that CB1Rs are highly expressed in PV interneurons across
several auditory nuclei. The functions of CB1Rs are not solely
determined by their expression levels in specific neuronal
subpopulations but are also closely related to the downstream efficacy
of their G protein-dependent signaling and cell-type specific signaling
dynamics. For instance, in the hippocampus, where GABAergic neurons
express much higher levels of CB1Rs than glutamatergic neurons, the fact
that the G protein-dependent signaling of CB1Rs is less effective in
GABAergic neurons suggests that CB1Rs function can be modulated by
contextual factors beyond mere receptor density (Steindel et al., 2013).
Likewise, the capacity of CB1Rs to modulate neurotransmission and
synaptic plasticity is indeed influenced not only by their expression
levels in specific cell types but also by the distinct functional
properties of these cells (Huang and Paul, 2019).