Browsing by Subject "mPFC"

Now showing 1 - 3 of 3
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    Altered Excitability and Local Connectivity of mPFC-PAG Neurons in a Mouse Model of Neuropathic Pain
    (SfN, 2018) Cheriyan, John; Sheets, Patrick L.; Anesthesia, School of Medicine
    The medial prefrontal cortex (mPFC) plays a major role in both sensory and affective aspects of pain. There is extensive evidence that chronic pain produces functional changes within the mPFC. However, our understanding of local circuit changes to defined subpopulations of mPFC neurons in chronic pain models remains unclear. A major subpopulation of mPFC neurons project to the periaqueductal gray (PAG), which is a key midbrain structure involved in endogenous pain suppression and facilitation. Here, we used laser scanning photostimulation of caged glutamate to map cortical circuits of retrogradely labeled cortico-PAG (CP) neurons in layer 5 (L5) of mPFC in brain slices prepared from male mice having undergone chronic constriction injury (CCI) of the sciatic nerve. Whole-cell recordings revealed a significant reduction in excitability for L5 CP neurons contralateral to CCI in the prelimbic (PL), but not infralimbic (IL), region of mPFC. Circuit mapping showed that excitatory inputs to L5 CP neurons in both PL and IL arose primarily from layer 2/3 (L2/3) and were significantly reduced in CCI mice. Glutamate stimulation of L2/3 and L5 elicited inhibitory inputs to CP neurons in both PL and IL, but only L2/3 input was significantly reduced in CP neurons of CCI mice. We also observed significant reduction in excitability and L2/3 inhibitory input to CP neurons ipsilateral to CCI. These results demonstrating region and laminar specific changes to mPFC-PAG neurons suggest that a unilateral CCI bilaterally alters cortical circuits upstream of the endogenous analgesic network, which may contribute to persistence of chronic pain.
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    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 Science
    Background: 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.
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    Optogenetic Inhibition of the mPFC During Delay Discounting
    (2019-05) White, Shelby M.; Lapish, Christopher; Logrip, Marian; Czachowski, Cristine
    Impulsivity, or the tendency to act prematurely without foresight, has been linked to a diverse range of pathological conditions. Foresight refers to the ability to envision future rewards and events (i.e. prospectively sample) and has been associated with decreased impulsivity. One form of impulsivity is measured by the ability to delay gratification and is often studied in the framework of Delay Discounting (DD). DD provides the means to study impulsivity in a number of pathological conditions. However, whether impulsivity precedes the development of pathological states or results from the pathological state itself is not fully understood. This necessitates an understanding of neurobiological mechanisms contributing to decision making in both non-impulsive as well as impulsive populations of individuals. Animal models allow invasive techniques to be used to dissect the neurocircuitry involved in decision making. Given that the decision-making process is an ongoing process rather than an isolated event, optogenetics provide the temporal and spatial specificity necessary for evaluating brain region specific contributions to decision making in DD. In the present study, optogenetics were used to assess the contribution of the medial Prefrontal Cortex (mPFC), a brain region involved in ‘goal-directed’ behavior, in the planning of future choices (i.e. prospective plans) and subsequent measures of impulsivity in an adjusting amount DD procedure. Optogenetic inhibition of mPFC was conducted in Wistar rats during different epochs of a DD task in order to assess how mPFC affects planning behavior in a population of rat not considered to be highly impulsive. Although no direct effects on planning behavior (e.g. consistency) were observed, inhibiting mPFC after a trial has been initiated and directly before a choice was made (Epoch 2) was observed to increase measures of impulsivity in comparison to days where no optogenetic manipulation occurred in a delay-specific manner. This suggests that mPFC differentially contributes to decision making at different delays. A pattern of associations between choice latency, impulsivity, and consistency began to emerge for inactivation occurring in Epoch 2, suggesting that mPFC contributes to some aspect of planning choices during this epoch. Moreover, these results indicate that mPFC is involved in decision making in Wistar Rats. Understanding the direct role that mPFC plays in promoting choices of delayed rewards provides a neurobiological target for treatment aimed at reducing impulsivity in the clinical population.