Biology subjects

Parker, K. E.

Publications and source records attributed to Parker, K. E..

6 recordsLinked to original sources

bioRxiv2026

A Wireless Wearable Platform for Intravenous Drug Self-Administration in Freely Behaving Rats

Studying how drugs act on neuronal circuits requires delivering them with temporal precision while behavior proceeds undisturbed, a combination that tethered infusion systems cannot provide. We developed WEARIT (Wireless Equipment for Autonomous Rat Infusion Tasks), a wearable, tetherless infusion platform that gives freely moving rats intravenous access under either remote or closed-loop operant control. The device houses a reservoir, miniaturized pump, rechargeable battery and Bluetooth circuitry in a 3D-printed enclosure worn on the back. By measuring spontaneous locomotion, amphetamine-induced hyperlocomotion and food-reinforced operant responding, we show that WEARIT leaves these behaviors unchanged. Remotely triggered fentanyl infusions yielded reliable delivery with physiological responses confirmed by pulse oximetry, and self-administration acquisition and dose-response functions were comparable to conventional tethered systems. WEARIT removes a longstanding constraint on intravenous pharmacology, opening self-administration paradigms to naturalistic and enriched environments and to concurrent imaging or optogenetic manipulation of the circuits engaged by drug reinforcement.

neuroscience↗

bioRxiv2025

Heat-responsive dynamic shifts in alternative splicing of the coral Acropora cervicornis

Climate change has caused drastic declines in corals. As sessile organisms, response to shifting environmental conditions may include changes in gene expression, epigenetic modifications, or the microbiome, but as of yet, a common mechanism of stress response, alternative splicing (AS), has been underexplored in corals. Using short-term acute thermal stress assays, we investigated patterns of AS in the scleractinian coral Acropora cervicornis during response to and a subsequent overnight recovery phase from low (33), medium (35), and high (37) levels of heat stress. We find that 40% of the genomic gene set is subject to AS. Our findings demonstrate conserved and dynamic shifts in splicing profiles during the heat treatment and subsequent recovery phase. AS increased in response to heat stress and was primarily dominated by intron retention in specific classes of transcripts, including those related to splicing regulation itself. While AS returned to baseline levels post-exposure to low heat, AS persisted even after reprieve from higher levels of heat stress. Partial overlap of AS transcripts with differentially expressed genes suggests that AS may represent a distinct and previously underappreciated regulatory mechanism for thermal stress response in corals.

genomics↗

bioRxiv2024

Monosynaptic ventral tegmental area glutamate projections to the locus coeruleus enhance aversive processing

Distinct excitatory synaptic inputs to the locus coeruleus (LC) modulate behavioral flexibility. Here we identify a novel monosynaptic glutamatergic input to the LC from the ventral tegmental area (VTA). We show robust VTA axonal projections provide direct glutamatergic transmission to LC. Despite weak synaptic summation, optogenetic activation of these axons enhances LC tonic firing and facilitates real-time and conditioned aversive behaviors. We hypothesized this projection may modulate synaptic integration with other excitatory inputs. We then used coincident VTA-LC photostimulation with local electrical stimulation and observed enhanced LC burst induction. To determine whether this integration also occurs in vivo, we took an analogous approach measuring reward-seeking behavior during unpredictable probabilistic punishment. Here, glutamatergic VTA-LC photostimulation during a concurrent noxious stimulus did not delay reward-seeking behavior, but increased probability of task failure. Together, we identified a novel VTA-LC glutamatergic projection that drives concurrent synaptic summation during salient stimuli to promote behavioral avoidance.

neuroscience↗

bioRxiv2023

Aging reduces motivation through decreased Bdnf expression in the ventral tegmental area

Age-associated reduced motivation is a hallmark of neuropsychiatric disorders in the elderly. In our rapidly aging societies, it is critical to keep motivation levels high enough to promote healthspan and lifespan. However, how motivation is reduced during aging remains unknown. Here, we used multiple mouse models to evaluate motivation and related affective states in young and old mice. We also compared the effect of social isolation, a common stressor in aged populations, to those of aging. We found that both social isolation and aging decreased motivation in mice, but that Bdnf expression in the ventral tegmental area (VTA) was selectively decreased during aging. Furthermore, VTA-specific Bdnf knockdown in young mice recapitulated reduced motivation observed in old mice. These results demonstrate that maintaining Bdnf expression in the VTA could promote motivation to engage in effortful activities and potentially prevent age-associated neuropsychiatric disorders.

neuroscience↗

bioRxiv2022

Punishment Risk Task: Monitoring anxiogenic states during goal directed actions in mice

Summary/AbstractCanonical preclinical studies of anxiety-related behavioral states use exploration of novel spaces to test approach-avoidance conflicts such as the open field test, elevated plus maze, and light-dark box. However, these assays cannot evaluate complicated behaviors in which competing states of motivation result in anxiogenic behaviors. Furthermore, these assays can only test the approach-avoidance conflict once due to a reliance on spatial novelty. Here we demonstrate the punishment risk task (PRT) in male and female, group- and singly-housed mice, a model initially described in singly-housed male rats by Park and Moghaddam (2017). The task tests how probabilistic punishment affects reward-seeking behavior. In particular, it measures the delay to pursue a reward (sweetened food pellet) while the likelihood of punishment (foot shock) actively impinges reward-associated actions. Here, we found that mice show increased latency to respond to food reward cues in trials in which the probability of punishment is highest. Further, anxiolytic treatment with diazepam or propranolol block any increase in response latency, indicating the models potential to for study of anxiogenesis in mice. Elucidating how these competitive behavioral states are integral to adaptive behavior and change over time and experience to coordinate anxiogenesis should greatly benefit anxiety disorder research. Specifically, implementing this assay in mice will enable cell-type selective interrogation of these processes and further our understanding of the neural basis of anxiogenesis.

neuroscience↗

bioRxiv2021

A photoswitchable GPCR-based opsin for presynaptic silencing

Optical manipulations of genetically defined cell types have generated significant insights into the dynamics of neural circuits. While optogenetic activation has been relatively straightforward, rapid and reversible synaptic inhibition has been far more difficult to achieve. Instead of relying on unpredictable ion manipulations or slow photoactivatable toxins at axon terminals, we took a different approach to leverage the natural ability of inhibitory presynaptic GPCRs to silence synaptic transmission. Here we characterize parapinopsin (PPO), a photoswitchable non-visual opsin from lamprey pineal gland that couples to Gi/o-signaling cascades. PPO can be rapidly activated by pulsed blue light, switched off with amber light, and is effective for repeated or prolonged inhibition. We developed viral vectors for cell-specific expression of PPO, which traffics very effectively in numerous neuron types. At presynaptic terminals, PPO can silence glutamate release and suppress dopamine-dependent reward and cocaine place preference behaviors in vivo. PPO immediately fills a significant gap in the neuroscience toolkit for rapid and reversible synaptic inhibition, and has broader utility for achieving spatiotemporal control of inhibitory GPCR signaling cascades in other biological and pharmacological applications.

neuroscience↗