Biology subjects

Mitten, E. H.

Publications and source records attributed to Mitten, E. H..

3 recordsLinked to original sources

bioRxiv2026

Unpredictable intermittent access exacerbates loss of control over ethanol drinking

BackgroundLoss of control over drinking is a hallmark feature of alcohol use disorder (AUD) that is modeled preclinically through escalation of ethanol consumption and aversion-resistant drinking. Prior work with other reinforcers suggests that within-session unpredictable, intermittent access (uIntA) promotes these phenotypes. However, the effect of uIntA on voluntary ethanol consumption is unknown. MethodsMale and female Long-Evans rats (n=9-10/group) underwent seven weeks of daily voluntary ethanol (20% v/v) drinking sessions under either a continuous access (ContA) or uIntA schedule. Following four weeks of baseline, rats were rendered dependent using a two-week chronic intermittent ethanol vapor exposure procedure. Daily testing was maintained through one week into withdrawal from vapor exposure. On the final day of testing, ethanol was adulterated with quinine (30 mg/L) to assess aversion-resistant drinking. ResultsRats drinking under ContA and uIntA exhibited similar levels of average daily ethanol consumption at baseline. However, uIntA elicited a more robust dependence-induced escalation of ethanol consumption compared to ContA, with uIntA sustaining escalation through early withdrawal. Additionally, while rats with ContA to ethanol remained sensitive to quinine even after chronic ethanol vapor exposure, uIntA promoted aversion-resistant drinking in ethanol dependent rats. ConclusionsThese results demonstrate that, compared to ContA, uIntA maintains ethanol drinking and exacerbates dependence-induced escalation and aversion-resistant ethanol consumption. This work positions uIntA as a powerful tool to assess psychological and neurobiological factors that may underlie loss of control over drinking.

neuroscience↗

bioRxiv2026

Functional bipartition of medial prefrontal cortex into salience detection and movement gain

Reward prediction error (RPE) is a key function putatively realized by brain-wide neural states to drive learning and adaptive responding. The medial prefrontal cortex (mPFC) is among the many areas canonically implicated in RPE computation. Yet, whether mPFC RPE processing differs as a function of valence, value, and sign is not well-understood. Here, we performed in vivo mPFC calcium imaging in male and female rats engaged in an appetitive or aversive Pavlovian task designed to elicit RPE, along with continuous, unbiased behavioral monitoring. We found that short-latency bulk mPFC activity reports salience independent of valence, value, or RPE. Surprisingly, as subsequently validated with in vivo bidirectional optogenetics, we show that salience-null mPFC activity modulates generalized movement in a valence- and task-agnostic fashion. Together, these results challenge the pervasive notion of a unitary, region-wide representation of cognitive processes, including RPE signaling, by bulk mPFC activity, and instead, support a functional bipartition schema combining reactive detection of integrated salience and dynamic modulation of movement gain.

neuroscience↗

bioRxiv2026

AAV-only targeting of ventral tegmental area dopamine neurons for optical self-stimulation studies in mice

Studies employing optogenetic approaches in rodent models have highlighted the important contribution of ventral tegmental area (VTA) dopamine (DA) neurons to reward, learning, and motivation. Selective manipulation of VTA DA neurons is generally achieved in these studies using transgenic mouse or rat lines that express Cre recombinase under the control of a promoter active in DA neurons, combined with intra-VTA infusion of adeno-associated virus (AAV) vectors harboring Cre recombinase-dependent expression cassettes. Reliance on transgenic Cre driver lines is expensive and decreases study efficiency, and available driver lines have unique limitations. Here, we report the development of an AAV-only approach that permits genetic access to VTA DA neurons and can support optogenetic self-stimulation in mice. We used a 2.5 kb fragment of the mouse tyrosine hydroxylase promoter (mTH) to drive Cre expression in VTA DA neurons. Intra-VTA co-infusion of AAV8-mTH-Cre with an AAV vector harboring a Cre-dependent yellow fluorescent protein expression cassette yielded high efficiency (82%) and high fidelity (73%) targeting of tyrosine hydroxylase-positive VTA neurons in C57BL/6J mice. Co-infusion of AAV8-mTH-Cre with a vector harboring a Cre-dependent channelrhodopsin (ChR2) expression cassette permitted optical regulation of VTA neurons with electrophysiological features consistent with VTA DA neurons. Moreover, C57BL/6J mice expressing ChR2 in VTA DA neurons rapidly acquired optical self-stimulation behavior. Thus, this AAV-only approach should facilitate investigation of VTA DA neuron contributions to reward-related behaviors and permit comparative assessments in reward circuit function in inbred and mutant mouse strains.

neuroscience↗