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Dopaminergic Neuromodulation of the Inducible Transcription Factor NPAS4


The brain converts fleeting experiences into long lasting changes in circuit connectivity and function. Activity induced immediate early genes(IEGs) are rapidly expressed in response to cellular stimuli. When a mouse is placed in an enriched environment, the inducible transcription factor(ITF) NPAS4 is expressed in hippocampal CA1 pyramidal neurons in response to depolarization and not other types of stimuli (Lin et al., 2008; Bloodgood et al., 2013). Expression of NPAS4 is further known to mediate inhibitory circuit rewiring onto pyramidal neurons through an increase in somatic inhibition by CCK basket cells and a decrease in dendritic inhibition (Bloodgood et al., 2013; Hartzell et al., 2018). Inhibitory circuit reorganization in CA1 through depolarization-dependent NPAS4 expression is likely to play an important functional role in encoding pyramidal cell place fields (Del Pino et al., 2017; Wilson et al., 2001; Danielson et al., 2016). However, the role of neuromodulatory inputs on NPAS4 expression an animal experiences in vivo is unknown. Neuromodulators such as dopamine, acetylcholine and noradrenaline are known to be released during periods of attention, novelty, and salience which an animal experiences as it travels through an enriched environment (Avery et al., 2017). With bath application of D1 dopamine receptor agonist SKF81297 on mouse acute slices, we show diminished NPAS4 expression in hippocampal CA1 pyramidal neurons. This result describes potential for dopamine to modulate NPAS4 mediated changes in inhibitory circuit connectivity in vivo and place field formation as the animal explores an enriched environment.

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