Biology subjects

Bass, C. E.

Publications and source records attributed to Bass, C. E..

7 recordsLinked to original sources

bioRxiv2026

Lateral hypothalamic melanin-concentrating hormone neuron dynamics in rats during sensory stimulation and sugar sweetened alcoholic cocktail drinking

There is a dearth of information on how different cocktails sweetened with different sugars impact brain activity. Glucose enters the brain faster and in greater concentration than fructose and directly affects neuronal activity of melanin-concentrating hormone (MCH) neurons. MCH signaling promotes both glucose drinking and alcohol intake by integrating central and sensory inputs, but it is currently unknown how MCH neuronal activity relates to sweetened cocktail drinking. This study sought to investigate the relationship between MCH activity and sugar-sweetened alcoholic cocktail drinking. We also sought to compare MCH neuronal responses to the sugar solutions without alcohol as well as their response to sensory stimuli. In female and male rats, we used fiber photometry to monitor MCH neurons in response to sensory stimuli and during drinking of 10% glucose, 10% fructose, and glucose or fructose cocktails with 1.25% or 10% alcohol. We found that MCH activity rises in response to a variety of sensory stimuli and peaks before the start of drinking for all cocktails, before returning to baseline near the start of drinking. The cocktail type impacted the dynamics of MCH activity, where increased alcohol concentration resulted in earlier MCH activity for fructose but not glucose cocktails. Finally, we found that peak MCH activity during drinking is correlated with approach behavior for all sugar and cocktail types. These findings suggest that glucose and alcohol may interact to directly influence MCH activity. Further, MCH neurons may regulate cocktail drinking in response to sugar type and alcohol concentration. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC="FIGDIR/small/719280v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@54685org.highwire.dtl.DTLVardef@59003eorg.highwire.dtl.DTLVardef@11f0358org.highwire.dtl.DTLVardef@114b524_HPS_FORMAT_FIGEXP M_FIG C_FIG New and noteworthyFiber photometry was used to monitor lateral hypothalamic melanin-concentrating hormone (MCH) neurons in male and female rats during sensory stimuli and drinking of glucose, fructose, or glucose- or fructose-sweetened alcoholic cocktails. Subsecond-scale changes in MCH activity occurred after stimuli. Peak MCH activity during drinking was correlated with approach behavior. Alcohol concentration only impacted MCH activity with fructose cocktails. We discuss the implications of MCH dynamics towards brain function, associative learning, and alcohol use disorder.

neuroscience↗

bioRxiv2024

Decoding mesolimbic dopamine transmission in the olfactory tubercle and its contribution to methamphetamine responses through neurochemical sensing and chemogenetics

Central dopamine (DA) innervation of the olfactory tubercle (OT) from the ventral tegmental area (VTA) plays a critical role in encoding multisensory information and generating behavioral outputs necessary for survival. However, due to anatomical restrictions and the neurochemical heterogeneity of the VTA and OT, very little is known about the functional link between mesolimbic VTA-DA transmission in the OT and its role in mediating reward and drug seeking. In this study, we integrated in vivo fast-scan cyclic voltammetry with chemogenetics to (1) characterize the effects of chemogenetic modulation (excitation and inhibition) of mesolimbic DA transmission in the OT of both anesthetized and awake-behaving wild-type rats and (2) demonstrate that inhibition of VTA-DA neurons is sufficient to suppress methamphetamine-induced DA transmission as well as its locomotor and rewarding effects. These results offer novel insights into mesolimbic DA transmission in the OT and its contribution to substance use disorders.

neuroscience↗

bioRxiv2020

Activation of VTA GABA Neurons Disrupts Reward Seeking by Altering Temporal Processing

The role of ventral tegmental area (VTA) dopamine in reward, cue processing, and interval timing is well characterized. Using a combinatorial viral approach to target activating DREADDs (Designer Receptors Exclusively Activated by Designer Drugs, hM3D) to GABAergic neurons in the VTA of male rats, we previously showed that activation disrupts responding to reward-predictive cues. Here we explored how VTA GABA neurons influence the perception of time in two fixed interval (FI) tasks, one where the reward or interval is not paired with predictive cues (Non-Cued FI), and another where the start of the FI is signaled by a constant tone that continues until the rewarded response is emitted (Cued FI). Under vehicle conditions in both tasks, responding was characterized by "scalloping" over the 30s FI, in which responding increased towards the end of the FI. However, when VTA GABA neurons were activated in the Non-Cued FI, the time between the end of the 30s interval and when the rats made a reinforced response increased. Additionally, post-reinforcement pauses and overall session length increased. In the Cued FI task, VTA GABA activation produced erratic responding, with a decrease in earned rewards. Thus, while both tasks were disrupted by VTA GABA activation, responding that is constrained by a cue was more sensitive to this manipulation, possibly due to convergent effects on timing and cue processing. Together these results demonstrate that VTA GABA activity disrupts the perception of interval timing, particularly when the timing is set by cues.

neuroscience↗

bioRxiv2020

Chemogenetic activation of mesoaccumbal Gamma-Aminobutyric Acid projections selectively tunes responses to predictive cues when reward value is unexpectedly decreased

BackgroundMesolimbic circuits regulate the attribution of motivational significance to incentive cues that predict reward, yet this network also plays a key role in adapting reward-seeking behavior when the contingencies linked to a cue unexpectedly change. Here we asked whether mesoaccumbal gamma-aminobutyric acid (GABA) projections enhance adaptive responding to incentive cues of abruptly altered reward value, and whether these effects were distinct from global activation of all ventral tegmental area (VTA) GABA circuits. MethodsWe used a viral targeting system to chemogenetically activate mesoaccumbal GABA projections in male rats during a novel cue-dependent operant Value Shifting (VS) task, in which the volume of a sucrose reward associated with a predictive cue is suddenly altered, from the beginning and throughout the session. We compared the results with global activation of VTA GABA neurons, which will activate local inhibitory circuits and long loop projections. ResultsWe found that activation of mesoaccumbal GABA projections decreases responding to incentive cues associated with smaller-than-expected rewards. This tuning of behavioral responses was specific to cues associated with smaller-than-expected rewards, but did not impact measures related to consuming the reward. In marked contrast, activating all VTA(GABA) neurons resulted in a uniform decrease in responding to incentive cues irrespective of changes in the size of the reward. ConclusionsTargeted activation of mesoaccumbal GABA neurons facilitate adaptation in reward-seeking behaviors. This suggests that these projections may play a very specific role in associative learning processes.

neuroscience↗

bioRxiv2020

Enhancing GABAergic Tone in the Rostral Nucleus of the Solitary Tract Reconfigures Sensorimotor Neural Activity

Recent work has shown that most cells in the rostral, gustatory portion of the nucleus tractus solitarius (rNTS) in awake, freely licking rats show lick-related firing. However, the relationship between taste-related and lick-related activity in rNTS remains unclear. Here, we tested if GABA-derived inhibitory activity regulates the balance of lick- and taste-driven neuronal activity. Combinatorial viral tools were used to restrict expression of ChR2-EYFP to GAD1+ GABAergic neurons. Viral infusions were bilateral in rNTS. 2-4wks later, an optical fiber attached to 8-16 drivable microwires was implanted into the rNTS. After recovery, water-deprived rats were presented with taste stimuli in an experimental chamber. Trials were 5 consecutive taste licks [NaCl, KCl, NH4Cl, sucrose, MSG/IMP, citric acid, quinine, or artificial saliva (AS)] separated by 5 AS licks on a VR5 schedule. Each taste lick triggered a 1s train of laser light (25Hz; 473nm; 8-10mW) in a random half of the trials. In all, 113 cells were recorded in the rNTS, 50 responded to one or more taste stimuli without GABA enhancement. Selective changes in response magnitude (spike count) within cells shifted across unit patterns but preserved inter-stimulus relationships. Cells where enhanced GABAergic tone increased lick coherence conveyed more information distinguishing basic taste qualities and different salts than other cells. In addition, GABA activation significantly amplified the amount of information that discriminated palatable vs. unpalatable tastants. By dynamically regulating lick coherence and remodeling the across-unit response patterns to taste, enhancing GABAergic tone in rNTS reconfigures the neural activity reflecting sensation and movement. Significance StatementThe rostral nucleus tractus solitarius (rNTS) is the first structure in the central gustatory pathway. Electrophysiological recordings from the rNTS in awake, freely-licking animals show that cells in this area have lick- as well as taste-related activity, but the relationship between these characteristics is not well understood. Here, we showed evidence that GABA activation can dynamically regulate both of these two properties in rNTS cells to enhance the information conveyed, especially about palatable vs. unpalatable tastants. These data provide insights into the role of inhibitory activity in the rNTS.

neuroscience↗

bioRxiv2019

Effects of hM4Di activation in CamKII basolateral amygdala neurons and CNO treatment on Sensory-Specific vs. General-PIT; refining PIT circuits and considerations for using CNO.

Pavlovian stimuli can influence instrumental behaviors, a phenomenon known as Pavlovian-to-instrumental transfer (PIT). PIT arises via psychologically and neurobiologically independent processes as Sensory-Specific-PIT (SS-PIT) and General-PIT. SS-, but not General-PIT, relies on the basolateral amygdala (BLA), however the specific BLA neuronal populations involved are unknown. Therefore, here we determined the contribution of glutamatergic BLA neurons to SS-PIT. The BLA was transduced with virus containing either GFP or hM4Di, driven by the CamKII promoter. Rats were then tested for SS- and General-PIT following Vehicle or Clozapine-n-oxide (CNO, the hM4Di-activating ligand) injection. CNO had no effect on SS-PIT in the GFP control group, but selectively blocked its expression in the hM4Di-expressing group. Furthermore, CNO did not alter the expression of Pavlovian outcome devaluation effects in GFP or hM4Di expressing groups, indicating that the hM4Di-mediated loss of SS-PIT did not result from an inability to recall the sensory-specific details of the Pavlovian stimulus-outcome associations. Unexpectedly, CNO disrupted General-PIT in both GFP and hM4Di expressing groups, indicating that CNO alone is sufficient to disrupt affective, but not sensory-specific processes. Disruption of General-PIT by CNO was not due to generalized motor effects, but instead may be related to shifts in internal state produced by CNO. Together these data identify BLA CamKII neurons as critical for the expression of SS-PIT, and reveal important considerations for using CNO to study general affective motivation.

neuroscience↗

bioRxiv2018

Exendin-4 disrupts responding to reward predictive incentive cues in rats

Exendin-4 (EX4) is a GLP-1 receptor agonist used clinically to control glycemia in Type-2 Diabetes Mellitus (T2DM), with the additional effect of promoting weight loss. The weight loss seen with EX4 is attributable to the varied peripheral and central effects of GLP-1, with contributions from the mesolimbic dopamine pathway that are implicated in cue-induced reward seeking. GLP-1 receptor agonists reduce preference for palatable foods (i.e. sweet and fat) as well as the motivation to obtain and consume these foods. Accumulating evidence suggest that GLP-1 receptor activity can attenuate cue-induced reward seeking behaviors. In the present study, we tested the effects of EX4 (0.6, 1.2, and 2.4 {micro}g/kg i.p.) on incentive cue (IC) responding. This rat model required rats to emit a nosepoke response during an intermittent audiovisual cue to obtain a sucrose reward (10% solution). EX4 dose-dependently attenuated responding to reward predictive cues, and increased latencies of the cue response and reward cup entry to consume the sucrose reward. Moreover, EX4 dose-dependently decreased the number of nosepokes relative to the number of cue presentations during the session. There was no drug effect on the number of reward cup entries per reward earned during the session, a related reward-seeking behavior with similar locomotor demand. Interestingly, there was a dose-dependent effect of time on the responding to reward predictive cues and nosepoke response latency, such that 2.4 {micro}g/kg of EX4 delayed responding to the initial IC of the behavioral session. Together, these findings suggest that agonism of the GLP-1 receptor with EX4 modulates the incentive properties of cues attributed with motivational significance.

pharmacology and toxicology↗