Behavioral and transcriptome alterations in male and female mice with postnatal deletion of TrkB in dorsal striatal medium spiny neurons

Abstract

BackgroundThe high affinity tyrosine kinase receptor, TrkB, is the primary receptor for brain derived neurotrophic factor (BDNF) and plays an important role in development, maintenance and plasticity of the striatal output medium size spiny neuron. The striatal BDNF/TrkB system is thereby implicated in many physiologic and pathophysiologic processes, the latter including mood disorders, addiction, and Huntington’s disease. We crossed a mouse harboring a transgene directing cre-recombinase expression primarily to postnatal, dorsal striatal medium spiny neurons, to a mouse containing a floxed TrkB allele (fB) mouse designed for deletion of TrkB to determine its role in the adult striatum.ResultsWe found that there were sexually dimorphic alterations in behaviors in response to stressful situations and drugs of abuse. Significant sex and/or genotype differences were found in the forced swim test of depression-like behaviors, anxiety-like behaviors on the elevated plus maze, and cocaine conditioned reward. Microarray analysis of dorsal striatum revealed significant dysregulation in individual and groups of genes that may contribute to the observed behavioral responses and in some cases, represent previously unidentified downstream targets of TrkB.ConclusionsThe data point to a set of behaviors and changes in gene expression following postnatal deletion of TrkB in the dorsal striatum distinct from those in other brain regions.

BDNF Controls Bidirectional Endocannabinoid Plasticity at Corticostriatal Synapses

“…Emerging evidences suggest that the brain-derived neurotrophic factor (BDNF) and its receptor, the tropomyosine receptor kinase B (TrkB) (Deinhardt and Chao, 2014), are strongly involved in shaping striatal functions (Baydyuk et al, 2011;Besusso et al, 2013;Unterwald et al, 2013;Jing et al, 2017). In addition, alterations of BDNF/TrkB signaling have been observed in several psychiatric and neurodegenerative disorders (Zuccato and Cattaneo, 2009;Autry and Monteggia, 2012).…”

Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice

“…Genetic modulation of BDNF or its receptor, TrkB, alters the rewarding effect of drugs of abuse such as cocaine and alcohol, [8][9][10] linking BDNF to addiction. Smoking also increases plasma BDNF levels in humans 11,12 and administered nicotine increases BDNF gene expression in critical regions of the mesolimbic reward circuit of rodents.…”

BDNF controls bidirectional endocannabinoid-plasticity at corticostriatal synapses

“…Synaptic plasticity is tightly controlled by various neuromodulators, also called the third factor (Foncelle et al, 2018), among which, BDNF appears to be indispensable for striatal functions (Baydyuk et al, 2011;Besusso et al, 2013;Unterwald et al, 2013). Indeed, in addition to its prominent role in inducing neuronal proliferation and differentiation, migration and survival, BDNF is a key regulator of synaptic transmission and plasticity in the adult brain (Carvalho et al, 2008;Waterhouse and Xu, 2009;Edelmann et al, 2014;Park et al, 2014).…”

“…In the dorsal striatum very low levels of BDNF have been reported and the striatal output neurons, the medium-sized spiny neurons (MSNs), do not show detectable level of BDNF mRNA (Altar et al, 1997;. However, MSNs display high levels of TrkB (Baydyuk et al, 2011;Besusso et al, 2013;Unterwald et al, 2013). Striatal BDNF is mainly released from glutamatergic cortical afferents (Altar et al, 1997;Jia et al, 2010).…”