Biology subjects

Alizo Vera, V.

Publications and source records attributed to Alizo Vera, V..

3 recordsLinked to original sources

bioRxiv2024

The GluA1 cytoplasmic tail regulates intracellular AMPA receptor trafficking and synaptic transmission onto dentate gyrus GABAergic interneurons, gating response to novelty

The GluA1 subunit, encoded by the putative schizophrenia-associated gene GRIA1, is required for activity-regulated AMPA receptor (AMPAR) trafficking, and plays a key role in cognitive and affective function. The cytoplasmic, carboxy-terminal domain (CTD) is the most divergent region across AMPAR subunits. The GluA1 CTD has received considerable attention for its role during long-term potentiation (LTP) at CA1 pyramidal neuron synapses. However, its function at other synapses and, more broadly, its contribution to different GluA1-dependent processes, is poorly understood. Here, we used mice with a constitutive truncation of the GluA1 CTD to dissect its role regulating AMPAR localization and function as well as its contribution to cognitive and affective processes. We found that GluA1 CTD truncation affected AMPAR subunit levels and intracellular trafficking. {Delta}CTD GluA1 mice exhibited no memory deficits, but presented exacerbated novelty-induced hyperlocomotion and dentate gyrus granule cell (DG GC) hyperactivity, among other behavioral alterations. Mechanistically, we found that AMPAR EPSCs onto DG GABAergic interneurons were significantly reduced, presumably underlying, at least in part, the observed changes in neuronal activity and behavior. In summary, this study dissociates CTD-dependent from CTD-independent GluA1 functions, unveiling the GluA1 CTD as a crucial hub regulating AMPAR function in a cell type-specific manner.

neuroscience↗

bioRxiv2024

Adolescent THC impacts on mPFC dopamine-mediated cognitive processes in male and female rats

RationaleAdolescent cannabis use is linked to later-life changes in cognition, learning, and memory. Rodent experimental studies suggest {Delta}9-tetrahydrocannabinol (THC) influences development of circuits underlying these processes, especially in the prefrontal cortex, which matures during adolescence. ObjectiveWe determined how 14 daily THC injections (5mg/kg) during adolescence persistently impacts medial prefrontal cortex (mPFC) dopamine-dependent cognition. MethodsIn adult Long Evans rats treated as adolescents with THC (AdoTHC), we quantify performance on two mPFC dopamine-dependent reward-based tasks--strategy set shifting and probabilistic discounting. We also determined how acute dopamine augmentation with amphetamine (0, 0.25, 0.5 mg/kg), or specific chemogenetic stimulation of ventral tegmental area (VTA) dopamine neurons and their projections to mPFC impacts probabilistic discounting. ResultsAdoTHC sex-dependently impacts acquisition of cue-guided instrumental reward seeking, but has minimal effects on set-shifting or probabilistic discounting in either sex. When we challenged dopamine circuits acutely with amphetamine during probabilistic discounting, we found reduced discounting of improbable reward options, with AdoTHC rats being more sensitive to these effects than controls. In contrast, neither acute chemogenetic stimulation of VTA dopamine neurons nor pathway-specific chemogenetic stimulation of their projection to mPFC impacted probabilistic discounting in control rats, although stimulation of this cortical dopamine projection slightly disrupted choices in AdoTHC rats. ConclusionsThese studies confirm a marked specificity in the cognitive processes impacted by AdoTHC exposure. They also suggest that some persistent AdoTHC effects may alter amphetamine-induced cognitive changes in a manner independent of VTA dopamine neurons or their projections to mPFC.

animal behavior and cognition↗

bioRxiv2022

Infralimbic projections to the nucleus accumbens shell and amygdala regulate the encoding of cocaine extinction learning

Prior evidence indicates that the infralimbic cortex (IL) mediates the ongoing inhibition of cocaine seeking following self-administration and extinction training in rats, specifically through projections to the nucleus accumbens (NA) shell. Our own data indicate that IL activity immediately following an unreinforced lever press is critical for encoding the extinction contingencies in such procedures. Whether extinction encoding requires activity in the IL exclusively or also activity in its outputs, such as those to the NAshell and amygdala, is unknown. To address this issue, we used a closed-loop optogenetic approach in female and male Sprague-Dawley rats to silence IL-NAshell or IL-amygdala activity following an unreinforced lever press during extinction training. Optical illumination (20 s) was given either immediately after a lever press or following a 20 s delay. IL-NAshell inhibition immediately following an unreinforced lever press increased lever pressing during extinction training and impaired retention of extinction learning, as assessed during subsequent extinction sessions without optical inhibition. Likewise, IL-amygdala inhibition given in the same manner impaired extinction retention during sessions without inhibition. Control experiments indicate that critical encoding of extinction learning does not require activity in these pathways beyond the initial 20 s post-lever press period, as delayed IL-NAshell and IL-amygdala inhibition had no effect on extinction learning. These results suggest that a larger network extending from the IL to the NAshell and amygdala is involved in encoding extinction contingencies following cocaine self-administration. Significance StatementInfralimbic cortex (IL) activity following an unreinforced lever press during extinction learning encodes the extinction of cocaine-seeking behavior. However, the larger circuitry controlling such encoding has not been investigated. Using closed-loop optogenetic pathway targeting, we found that inhibition of IL projections to the nucleus accumbens (NA) shell and to the amygdala impaired the extinction of cocaine seeking. Importantly, these effects were only observed when activity was disrupted during the first 20 s post-lever press and not when given following a 20 s delay. These findings suggest that successful cocaine extinction encoding requires activity across a larger circuit beyond simply inputs to the IL.

neuroscience↗