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Browsing by Author "Morningstar, Mitchell D."
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Item Ethanol Alters Variability, But Not Rate, of Firing in Medial Prefrontal Cortex Neurons of Awake-Behaving Rats(Wiley, 2020-11) Morningstar, Mitchell D.; Linsenbardt, David N.; Lapish, Christopher C.; Psychology, School of ScienceBackground: The medial prefrontal cortex (mPFC) is a brain region involved in the evaluation and selection of motivationally relevant outcomes. Neural activity in mPFC is altered following acute ethanol (EtOH) use and, in rodent models, doses as low as 0.75 g/kg yield cognitive deficits. Deficits in decision making following acute EtOH are thought to be mediated, at least in part, by decreases in mPFC firing rates (FRs). However, the data leading to this conclusion have been generated exclusively in anesthetized rodents. The present study characterizes the effects of acute EtOH injections on mPFC neural activity in awake-behaving rodents. Methods: Awake-behaving and anesthetized in vivo electrophysiological recordings were performed. We utilized 3 groups: the first received 2 saline injections, the second received a saline injection followed by 1.0 g/kg EtOH, and the last received saline followed by 2 g/kg EtOH. One week later, an anesthetized recording occurred where a saline injection was followed by an injection of 1.0 g/kg EtOH. Results: The anesthetized condition showed robust decreases in neural activity and differences in up-down states (UDS) dynamics. In the awake-behaving condition, FRs were grouped according to behavioral state: moving, not-moving, and sleep. The differences in median FRs were found for each treatment and behavioral state combination. A FR decrease was only found in the 2.0 g/kg EtOH treatment during not-moving states. However, robust decreases in FR variability were found across behavioral state in both the 1.0 and 2.0 g/kg EtOH treatment. Sleep was separately analyzed. EtOH modulated the UDS during sleep producing decreases in FRs. Conclusions: In conclusion, the changes in neural activity following EtOH administration in anesthetized animals are not conserved in awake-behaving animals. The most prominent difference following EtOH was a decrease in FR variability suggesting that acute EtOH may be affecting decision making via this mechanism.Item Impact of Acute Ethanol Injections on Medial Prefrontal Cortex Neural Activity(2019-12) Morningstar, Mitchell D.; Lapish, Christopher; Goodlett, Charles; Linsenbardt, DavidThe medial prefrontal cortex (mPFC) is a cortical brain region involved in the evaluation and selection of motivationally relevant outcomes. mPFC-mediated cognitive functions are impaired following acute alcohol exposure. In rodent models, ethanol (EtOH) doses as low as 0.75 g/kg yield deficits in cognitive functions. These deficits following acute EtOH are thought to be mediated, at least in part, by decreases in mPFC firing rates. However, these data have been generated exclusively in anesthetized rodents. To eliminate the potentially confounding role of anesthesia on EtOH modulated mPFC activity, the present study investigated the effects of acute EtOH injections on mPFC neural activity in awake-behaving rodents. We utilized three groups: the first group received 2 saline injections during the recording. The second group received a saline injection followed 30 minutes later by a 1.0 g/kg EtOH injection. The last group received a saline injection followed 30 minutes later by a 2.0 g/kg EtOH injection. One week following the awake-behaving recording, an anesthetized recording was performed using one dose of saline followed 30 minutes later by one dose of 1.0 g/kg EtOH in order to replicate previous studies. Firing rates were normalized to a baseline period that occurred 5 minutes prior to each injection. A 5-minute time period 30 minutes following the injection was used to compare across groups. There were no significant differences across the awake-behaving saline-saline group, indicating no major effect on mPFC neural activity as a result of repeated injections. There was a significant main effect across treatment & behavioral groups in the saline-EtOH 1.0 g/kg group with reductions in the EtOH & Sleep condition. In the saline-EtOH 2.0 g/kg, mPFC neural activity was only reduced in lowered states of vigilance. This suggests that EtOH only causes gross changes on neural activity when the animal is not active and behaving. Ultimately this means that EtOH’s impact on decision making is not due to gross changes in mPFC neural activity and future work should investigate its mechanism.Item Impaired cognitive flexibility and heightened urgency are associated with increased alcohol consumption in rodent models of excessive drinking(Wiley, 2021) De Falco, Emanuela; White, Shelby M.; Morningstar, Mitchell D.; Ma, Baofeng; Nkurunziza, Lionnel T.; Ahmed-Dilibe, Anisah; Wellman, Cara L.; Lapish, Christopher C.; Psychology, School of ScienceAlcohol use disorder (AUD) is characterized by impairments in decision-making that can exist as stable traits or transient states. Cognitive inflexibility reflects an inability to update information that guides decision-making and is thought to contribute to the inability to abstain from drinking. While several studies have reported evidence of impaired cognitive flexibility following chronic alcohol exposure, evidence that a pre-existing impairment in cognitive flexibility is a heritable risk factor for AUD is scarce. Here, we found that cognitive flexibility was impaired in rodents selectively bred for excessive alcohol consumption (alcohol preferring (P) rats), on the attentional set-shifting task (ASST). Further, the degree of impairment is predictive of future ethanol consumption, thus suggesting that cognitive inflexibility is a stable trait capable of predisposing one for drinking. In a second set of experiments, we observed an impairment in the ability of P rats to use a previously learned rule to guide foraging in a simple discrimination task. Convergence across several behavioral measures suggested that this impairment reflected a state of heightened urgency that interfered with decision-making. A similar impairment on a simple discrimination task was observed in Wistar rats with a history of alcohol consumption. These findings indicate how trait and state variables-in this case, impaired cognitive flexibility and heightened urgency, respectively-may influence the risk for excessive drinking. Furthermore, our results suggest that cognitive inflexibility and urgency can exist as both risk factors for and the result of alcohol exposure.Item Proactive Versus Reactive Control Strategies Differentially Mediate Alcohol Seeking in Wistars and P Rats(2023-05) Morningstar, Mitchell D.; Lapish, Christopher; Czachowski, Cristine; Grahame, Nicholas; Brigman, JonathanProblematic alcohol consumption develops concurrently with deficits in decision-making. These deficits may be due to alterations in dorsal medial prefrontal cortex (dmPFC) neural activity, as it is essential for the evaluation and implementation of behavioral strategies. In this study, we hypothesized that differences in cognitive control would be evident between Wistars and alcohol-preferring P rats. Cognitive control can be split into proactive and reactive components. Proactive control maintains goal-directed behavior independent of a stimulus whereas reactive control elicits goal-directed behavior at the time of a stimulus. Specifically, it was hypothesized that Wistars would show proactive control over alcohol-seeking whereas P rats would show reactive control over alcohol-seeking. Proactive control in our rodent model is defined as responding to distal task cues whereas reactive control is responding to proximal cues. This was tested in rodents performing a 2-way Cued Access Protocol (2CAP) that facilitates measurements of alcohol seeking and drinking. Congruent sessions were the typical, default 2CAP sessions that consisted of the CS+ being on the same side as alcohol access. These were compared with incongruent sessions where alcohol access was opposite of the CS+. Wistars exhibited an increase in incorrect approaches during the incongruent sessions, which was not detectable in P rats. A trial-by-trial analysis indicated that the increases in incorrect responses was explained by Wistars utilizing the previously learned task-rule, whereas the P rats did not. This motivated the subsequent hypothesis that neural activity patterns corresponding to proactive control would be observable in Wistars but not P rats. Principal Component Analysis indicated that neural ensembles in the dmPFC of Wistars exhibited decreased activity to the cue light in incongruent sessions whereas P rat ensembles displayed increased activity at timepoints associated with the onset and end of alcohol access. Overall, it was observed that P rats showed the most differences in neural activity at times relevant for alcohol delivery; specifically, when the sipper came into the apparatus and left. Conversely, Wistars showed differences prior to approach as evidenced by both differences in cue-related activity as well as differences in spatial-strategies. Together, these results support our hypothesis that Wistars are more likely to engage proactive cognitive control strategies whereas P rats are more likely to engage reactive cognitive control strategies. Although P rats were bred to prefer alcohol, differences in cognitive control phenotypes may have concomitantly occurred that are of clinical relevance.Item Understanding ethanol's acute effects on medial prefrontal cortex neural activity using state-space approaches(Elsevier, 2021) Morningstar, Mitchell D.; Barnett, William H.; Goodlett, Charles R.; Kuznetsov, Alexey; Lapish, Christopher C.; Psychology, School of ScienceAcute ethanol (EtOH) intoxication results in several maladaptive behaviors that may be attributable, in part, to the effects of EtOH on neural activity in medial prefrontal cortex (mPFC). The acute effects of EtOH on mPFC function have been largely described as inhibitory. However, translating these observations on function into a mechanism capable of delineating acute EtOH's effects on behavior has proven difficult. This review highlights the role of acute EtOH on electrophysiological measurements of mPFC function and proposes that interpreting these changes through the lens of dynamical systems theory is critical to understand the mechanisms that mediate the effects of EtOH intoxication on behavior. Specifically, the present review posits that the effects of EtOH on mPFC N-methyl-d-aspartate (NMDA) receptors are critical for the expression of impaired behavior following EtOH consumption. This hypothesis is based on the observation that recurrent activity in cortical networks is supported by NMDA receptors, and, when disrupted, may lead to impairments in cognitive function. To evaluate this hypothesis, we discuss the representation of mPFC neural activity in low-dimensional, dynamic state spaces. This approach has proven useful for identifying the underlying computations necessary for the production of behavior. Ultimately, we hypothesize that EtOH-related alterations to NMDA receptor function produces alterations that can be effectively conceptualized as impairments in attractor dynamics and provides insight into how acute EtOH disrupts forms of cognition that rely on mPFC function. This article is part of the special Issue on 'Neurocircuitry Modulating Drug and Alcohol Abuse'.