Developmental but not adult cannabinoid treatments persistently alter axonal and dendritic morphology within brain regions important for zebra finch vocal learning

Gilbert, Marcoita T.; Soderstrom, Ken

doi:10.1016/j.brainres.2014.02.039

Cited by 5 publications

(3 citation statements)

References 52 publications

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“…Our results are in agreement with the increased density of axonal markers observed during the development of zebrafish treated with the CB1 agonist WIN55212-2 (Gilbert and Soderstrom, 2014). However, while these authors showed an increased density of dendritic proteins after CB1R activation during development (but not in adult), we did not detect CB1R expression in dendrites.…”

Section: Resultssupporting

confidence: 91%

Cannabinoid Receptors Modulate Neuronal Morphology and AnkyrinG Density at the Axon Initial Segment

Tapia

Dominguez

Zhang

et al. 2017

Front. Cell. Neurosci.

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Neuronal polarization underlies the ability of neurons to integrate and transmit information. This process begins early in development with axon outgrowth, followed by dendritic growth and subsequent maturation. In between these two steps, the axon initial segment (AIS), a subcellular domain crucial for generating action potentials (APs) and maintaining the morphological and functional polarization, starts to develop. However, the cellular/molecular mechanisms and receptors involved in AIS initial development and maturation are mostly unknown. In this study, we have focused on the role of the type-1 cannabinoid receptor (CB1R), a highly abundant G-protein coupled receptor (GPCR) in the nervous system largely involved in different phases of neuronal development and differentiation. Although CB1R activity modulation has been related to changes in axons or dendrites, its possible role as a modulator of AIS development has not been yet explored. Here we analyzed the potential role of CB1R on neuronal morphology and AIS development using pharmacological and RNA interference approaches in cultured hippocampal neurons. CB1R inhibition, at a very early developmental stage, has no effect on axonal growth, yet CB1R activation can promote it. By contrast, subsequent dendritic growth is impaired by CB1R inhibition, which also reduces ankyrinG density at the AIS. Moreover, our data show a significant correlation between early dendritic growth and ankyrinG density. However, CB1R inhibition in later developmental stages after dendrites are formed only reduces ankyrinG accumulation at the AIS. In conclusion, our data suggest that neuronal CB1R basal activity plays a role in initial development of dendrites and indirectly in AIS proteins accumulation. Based on the lack of CB1R expression at the AIS, we hypothesize that CB1R mediated modulation of dendritic arbor size during early development indirectly determines the accumulation of ankyrinG and AIS development. Further studies will be necessary to determine which CB1R-dependent mechanisms can coordinate these two domains, and what may be the impact of these early developmental changes once neurons mature and are embedded in a functional brain network.

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Section: Resultssupporting

confidence: 91%

Cannabinoid Receptors Modulate Neuronal Morphology and AnkyrinG Density at the Axon Initial Segment

Tapia

Dominguez

Zhang

et al. 2017

Front. Cell. Neurosci.

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“…Dramatic changes in CB1 receptor expression levels occur over normal zebra finch development: low densities are observed during the auditory learning stage (25 day olds); peak dense expression occurs during sensorimotor learning (50 and 75 days) and; levels wane to approximately that of the auditory stage in adulthood (>100 days, Soderstrom and Tian, 2006). Agonist treatment during this period also results in persistent changes to increase dendritic spine densities and expression of synaptic markers, suggesting that these changes are involved in the mechanism of cannabinoid-altered vocal learning (Gilbert and Soderstrom, 2014, 2011). …”

Section: Introductionmentioning

confidence: 98%

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

Holland

Soderstrom

2017

Brain Research

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During typical late-postnatal CNS development, net reductions in dendritic spine densities are associated with activity-dependent learning. Prior results showed agonist exposure in young animals increased spine densities in a subset of song regions while adult exposures did not, suggesting endocannabinoid signaling regulates dendritic spine dynamics important to vocal development. Here we addressed this question using the CB1 receptor-selective antagonist SR141716A (SR) to disrupt endocannabinoid signaling both during and after vocal learning. We hypothesized antagonist exposure during vocal development, but not adulthood, would alter spine densities. Following 25 days of exposure and a 25 day maturation period, 3D reconstructions of Golgi-Cox stained neurons were used to measure spine densities. We found antagonist treatments during both age periods increased densities within Area X (basal ganglia) and following adult treatments within HVC (premotor cortical-like). Results suggest both inappropriate cannabinoid receptor stimulation and inhibition are capable of similar disregulatory effects during establishment of circuits important to vocal learning, with antagonism extending these effects through adulthood. Given clinical evidence of depressant effects of SR, we tested the ability of the antidepressant monoamine oxidase inhibitor (MAOI) phenelzine to mitigate SR-induced spine density increases. This was confirmed implicating interaction between monoamine and endocannabinoid systems. Finally, we evaluated acute effects of these drugs to alter ability of novel song exposure to increase spine densities in auditory NCM and other regions, finding when combined, SR and phenelzine increased densities within Area X. These results contribute to understanding relevance of dendritic spine dynamics in neuronal development, drug abuse, and depression.

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“…Among CB 1 ‐mediated actions, cannabinoids inhibit the formation of new synapses in vitro (Kim & Thayer, 2001; Mulder et al., 2008) and deletion of CB 1 in GABAergic neurons enhances the number of GABAergic terminals in the neocortex and hippocampus (Berghuis et al., 2007). Appropriate activation and further signaling of CB 1 in GABAergic neurons are crucial during critical ages such as perinatal/postnatal ages or adolescence, when structural and functional remodeling of the brain are conspicuous (Scheyer et al 2019; Gilbert & Soderstrom, 2014). Indeed, non‐physiological activation of CB 1 in GABA cells at these ages may induce long‐lasting changes in brain activity and dysregulation of maturational processes modifying excitatory/inhibitory balance and associated cortical oscillatory states, potentially facilitating a subsequent appearance of epilepsy or schizophrenia (Cass et al., 2014; Volk & Lewis, 2005; Volk & Lewis, 2016; De Salas‐Quiroga et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Cannabinoid Receptor 1 associates to different molecular complexes during GABAergic neuron maturation

Molina‐Holgado

Paniagua‐Torija

Arévalo-Martı́n

et al. 2021

Journal of Neurochemistry

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CB1 cannabinoid receptor is widely expressed in the central nervous system of animals from late prenatal development to adulthood. Appropriate activation and signaling of CB1 cannabinoid receptors in cortical interneurons are crucial during perinatal/postnatal ages and adolescence, when long‐lasting changes in brain activity may elicit subsequent appearance of disorders in the adult brain. Here we used an optimized immunoprecipitation protocol based on specific antibodies followed by shot‐gun proteomics to find CB1 interacting partners in postnatal rat GABAergic cortical neurons in vitro at two different stages of maturation. Besides describing new proteins associated with CB1 like dihydrolipoyllysine‐residue acetyltransferase component of pyruvate dehydrogenase complex (DLAT), fatty acid synthase (FASN), tyrosine 3‐monooxygenase/tryptophan 5‐monooxygenase activation protein zeta (YWHAZ), voltage‐dependent anion channel 1 (VDAC1), myosin phosphatase Rho‐interacting protein (MPRIP) or usher syndrome type‐1C protein‐binding protein 1 (USHBP1), we show that the signaling complex of CB1 is different between maturational stages. Interestingly, the CB1 signaling complex is enriched at the more immature stage in mitochondrial associated proteins and metabolic molecular functions, whereas at more mature stage, CB1 complex is increased in maturation and synaptic‐associated proteins. We describe also interacting partners specifically immunoprecipitated with either N‐terminal or C‐terminal CB1 directed antibodies. Our results highlight new players that may be affected by altered cannabinoid signaling at this critical window of postnatal cortical development.

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Developmental but not adult cannabinoid treatments persistently alter axonal and dendritic morphology within brain regions important for zebra finch vocal learning

Cited by 5 publications

References 52 publications

Cannabinoid Receptors Modulate Neuronal Morphology and AnkyrinG Density at the Axon Initial Segment

Cannabinoid Receptors Modulate Neuronal Morphology and AnkyrinG Density at the Axon Initial Segment

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

Cannabinoid Receptor 1 associates to different molecular complexes during GABAergic neuron maturation

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