Biology subjects

Loney, G. C.

Publications and source records attributed to Loney, G. C..

4 recordsLinked to original sources

bioRxiv2026

Activation of basal forebrain cholinergic neurons promotes the attribution of incentive salience to reward cues in male rats

Background: Reward-associated environmental stimuli (cues) can gain incentive salience in some individuals, thereby becoming attractive, reinforcing, and instigators of motivational states. In rodents, the tendency to attribute incentive salience can be measured using a Pavlovian Conditioned Approach (PavCA) procedure, in which approach to a food cue (sign-tracking), relative to approach to the food delivery location (goal-tracking) is the operational definition of the incentive salience attributed to the cue. Growing evidence suggests that acetylcholine promotes this process, thus the current study tested the effect of activating cholinergic neurons in the basal forebrain on sign- and goal-tracking during PavCA. Methods: We injected a Cre-dependent virus with excitatory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) into the horizontal limb of the diagonal band of Broca of transgenic rats expressing cre-recombinase in acetylcholine containing neurons. We then injected clozapine-n-oxide (CNO) before each of eight sessions of PavCA. On the ninth session, no CNO was given to test if any effects were immediately reversible. Results: We found that activation of basal forebrain cholinergic neurons increased sign-tracking over time without an overall effect on goal-tracking, relative to a control group injected with a control virus. Changes in responding from the final CNO session to the saline test did not differ between virus groups. Conclusions: This effect demonstrates that acetylcholine promotes the attribution of incentive salience to a reward-related cue. Future studies should investigate the effect of inhibiting this area on sign-tracking as well as how activation of this area influences reactivity to cues associated with other rewards such as drugs of abuse.

neuroscience↗

bioRxiv2022

Escalation of alcohol intake is associated with regionally decreased insular cortex activity but not associated with changes in taste quality

BackgroundIntermittent access to ethanol (EtOH) drives persistent escalation of intake and rapid transition from moderate to compulsive-like drinking. Intermittent EtOH drinking may facilitate escalation in part by altering aversion-sensitive neural substrates, such as the insular cortex (IC), thus driving greater approach toward stimuli previously treated as aversive. MethodsWe conducted a series of experiments in rats to examine behavioral and neural responses associated with escalation of EtOH intake. First, taste reactivity analyses quantified the degree that intermittent brief-access ethanol exposure (BAEE) alters sensitivity to the aversive properties of EtOH. Next, we determined whether pharmacological IC inhibition facilitated EtOH escalation. Finally, given that IC is primary gustatory cortex, we employed psychophysical paradigms to assess whether escalation of EtOH intake induced changes in EtOH taste. These paradigms measured changes in sensitivity to the intensity of EtOH taste and whether escalation shifts the salient taste quality of EtOH by measuring the degree that the taste of EtOH generalized to a sucrose-like ( sweet) or quinine-like ( bitter) percept. ResultsWe found a near complete loss of aversive oromotor responses in EtOH-exposed relative to -naive rats. Additionally, we observed significantly reduced expression of EtOH-induced c-Fos expression in the posterior IC in exposed rats relative to naive rats. Inhibition of the IC resulted in a modest, but statistically reliable increase in acceptance of higher EtOH concentrations in naive rats. Finally, we found no evidence of changes in the psychophysical assessment of the taste of EtOH in exposed, relative to naive, rats. ConclusionsOur results demonstrate that neural activity within the IC adapts following escalation of EtOH intake in a manner that correlates with reduced sensitivity to the aversive hedonic properties of EtOH. These data further establish that IC may be driving exposure-induced escalations in EtOH intake and directly contributing to development of compulsive-like EtOH drinking.

neuroscience↗

bioRxiv2020

Nicotine and Opioid Polysubstance Abuse: Enhancement of opioid self-administration by systemic nicotine and modulation of opioid-associated memories by insular nicotine

Concurrent nicotine use is associated with increased liability for the development and exacerbation of opioid-use disorders. Habitual use of nicotine containing products increases propensity to misuse prescription opioids and its prevalence is substantially increased in individuals currently involved in opioid-treatment programs. Nicotine enhances self-administration of many classes of drugs in rodents, though evidence for direct effects on opioids is lacking. We sought to measure the effects of nicotine pretreatment on the reinforcing efficacy of opioids in both self-administration and contextual conditioning paradigms. First, we measured the effect of systemic nicotine pretreatment on self-administration of two opioids. Additionally, we measured the degree to which systemic nicotine pretreatment impacts the formation of morphine-associated contextual memories in conditioned taste avoidance and place preference paradigms. Given the involvement of the insula in the maintenance of substance abuse, its importance in nicotine addiction, and findings that insular inactivation impairs contextual drug conditioning, we examined whether nicotine administered directly to the insula could recapitulate the effects of systemic nicotine. We demonstrate that systemic nicotine pretreatment significantly enhances opioid self-administration and alters contextual conditioning. Furthermore, intra-insula nicotine similarly altered morphine contextual conditioning by blocking the formation of taste avoidance at all three morphine doses tested (5.0, 10, & 20 mg/kg), while shifting the dose-response curve of morphine in the place preference paradigm rightward. In conclusion, these data demonstrate that nicotine facilitates opioid intake and is partly acting within the insular cortex to obfuscate aversive opiate memories while potentiating approach to morphine-associated stimuli at higher doses.

neuroscience↗

bioRxiv2019

Multiple PLCβ signaling pathways in taste receptor cells contribute to the detection of bitter, sweet and umami stimuli

Taste receptor cells use multiple signaling pathways to detect chemicals in potential food items. These cells are functionally grouped into different types: Type I cells act as support cells and have glial-like properties; Type II cells detect bitter, sweet, and umami taste stimuli; and Type III cells detect sour and salty stimuli. We have identified a new population of taste cells that are broadly tuned to multiple taste stimuli including bitter, sweet, sour and umami. The goal of this study was to characterize these broadly responsive (BR) taste cells. We used an IP3R3-KO mouse (does not release calcium (Ca2+) from Type II cells when stimulated with bitter, sweet or umami stimuli) to characterize the BR cells without any potentially confounding input from Type II cells. Using live cell Ca2+ imaging in isolated taste cells from the IP3R3-KO mouse, we found that BR cells are a subset of Type III cells that respond to sour stimuli but also use a PLC{beta}3 signaling pathway to respond to bitter, sweet and umami stimuli. Unlike Type II cells, individual BR cells are broadly tuned and respond to multiple stimuli across different taste modalities. Live cell imaging in a PLC{beta}3-KO mouse confirmed that BR cells use a PLC{beta}3 signaling pathway to generate Ca2+ signals to bitter, sweet and umami stimuli. Analysis of c-Fos activity in the nucleus of the solitary tract (NTS) and short term behavioral assays revealed that BR cells make significant contributions to taste.

neuroscience↗