Novel song-stimulated dendritic spine formation and Arc/Arg3.1 expression in zebra finch auditory telencephalon are disrupted by cannabinoid agonism

Abstract

Cannabinoids are well-established to alter processes of sensory perception; however neurophysiological mechanisms responsible remain unclear. Arc, an immediate-early gene (IEG) product involved in dendritic spine dynamics and necessary for plasticity changes such as long-term potentiation, is rapidly induced within zebra finch caudal medial nidopallium (NCM) following novel song exposure, a response that habituates after repeated stimuli. Arc appears unique in its rapid postsynaptic dendritic expression following excitatory input. Previously, we found that vocal development-altering cannabinoid treatments are associated with elevated dendritic spine densities in motor- (HVC) and learning-related (Area X) song regions of zebra finch telencephalon. Given Arc’s dendritic morphological role, we hypothesized that cannabinoid-altered spine densities may involve Arc-related signaling. To test this, we examined the ability of the cannabinoid agonist WIN55212-2 (WIN) to: (1) acutely disrupt song-induced Arc expression; (2) interfere with habituation to auditory stimuli and; (3) alter dendritic spine densities in auditory regions. We found that WIN (3 mg/kg) acutely reduced Arc expression within both NCM and Field L2 in an antagonist-reversible manner. WIN did not alter Arc expression in thalamic auditory relay Nucleus Ovoidalis (Ov), suggesting cannabinoid signaling selectively alters responses to auditory stimulation. Novel song stimulation rapidly increased dendritic spine densities within auditory telencephalon, an effect blocked by WIN pretreatments. Taken together, cannabinoid inhibition of both Arc induction and its habituation to repeated stimuli, combined with prevention of rapid increases in dendritic spine densities, implicates cannabinoid signaling in modulation of physiological processes important to auditory responsiveness and memory.

Chronic CB1 cannabinoid receptor antagonism persistently increases dendritic spine densities in brain regions important to zebra finch vocal learning and production in an antidepressant-sensitive manner

“…Distinct roles for endocannabinoid signaling during different stages of mammalian neuronal development are well-documented (reviewed by Gaffuri et al, 2012) and we have previously seen these types of differential effects in our avian model (Gilbert and Soderstrom, 2013, 2011; Soderstrom et al, 2011). The present experiments demonstrate antagonist efficacy within Area X to increase spine density that is not restricted to development (Fig.…”

“…We reported earlier that novel song exposure also rapidly increases dendritic spine densities within NCM, and that this acute effect is blocked by a cannabinoid agonist (Gilbert and Soderstrom, 2013). We therefore hypothesized that the antagonist may also acutely alter spine densities in the song stimulation model.…”

“…The acute model that we used was the novel song exposure paradigm that had been used previously to show that novel song rapidly increases spine densities within auditory NCM (Gilbert and Soderstrom, 2013). These novel song-stimulated spine density increases demonstrated that cannabinoid signaling is able to modulate this sensory response, and that endocannabinoids may regulate it.…”

“…Based upon prior work establishing that song regions distinctly and densely express CB1 cannabinoid receptors, and that chronic cannabinoid agonism during sensorimotor vocal learning both alters song (Soderstrom and Johnson, 2003; Soderstrom and Tian, 2004) and increases dendritic spine densities in these regions (Gilbert and Soderstrom, 2013, 2011) we hypothesized that cannabinoid antagonism would produce opposing effects, and that these effects would be restricted to periods of development and not produced following adult treatments. We were surprised not to confirm these hypotheses, finding instead that antagonist exposure during both development and adulthood resulted in spine density increases within Area X, and within HVC following adult treatments (Fig.…”

“…In addition to comparing persistent effects of chronic treatments administered during development and in adulthood, we also evaluated acute effects of the drugs to alter responses following novel song exposure. We have used this approach previously to determine that CB1 activation interferes with the ability of novel song to rapidly increase dendritic spine densities within the auditory region, NCM (Gilbert and Soderstrom, 2013). Thus, the novel song paradigm provides a model system within which to study acute drug effects on dendritic spine dynamics.…”