RESUMEN
Although many studies have shown that the prelimbic (PL) cortex of the mPFC is involved in the formation of conditioned freezing behavior, few have considered the acoustic response characteristics of PL cortex. Importantly, the change in auditory response characteristics of the PL cortex after conditional fear learning is largely unknown. Here we used in vivo cell-attached recordings targeting the mPFC during the waking state. We confirmed that the mPFC of adult C57 mice have neurons that respond to noise and tone in the waking state, especially in the PL cortex. Interestingly, the data also confirmed that these neurons responded well to the intensity of sound but did not have frequency topological distribution characteristics. Furthermore, we found that the number of c-fos positive neurons in the PL cortex increased significantly after auditory fear conditioning. The auditory-induced local field potential recordings and in vivo cell-attached recordings demonstrated that the PL cortex was more sensitive to the auditory conditioned stimulus after the acquisition of conditioned fear. The proportion of neurons responding to noise was significantly increased, and the signal to noise ratio of the spikes were also increased. These data reveal that PL neurons themselves responded to the main information (sound intensity), while the secondary information (frequency) response was almost negligible after auditory fear conditioning. This phenomenon may be the functional basis for handling this type of emotional memory, and this response characteristic is thought to be emotional sensitization but does not change the nature of this response.
Asunto(s)
Miedo , Corteza Prefrontal , Animales , Condicionamiento Clásico , Memoria , Ratones , NeuronasRESUMEN
Withdrawal from extended-access cocaine self-administration leads to progressive intensification ('incubation') of cocaine craving. After prolonged withdrawal (1-2 months), when craving is high, expression of incubation depends on strengthening of excitatory inputs to medium spiny neurons (MSN) of the nucleus accumbens (NAc). These excitatory inputs interact with the intra-NAc GABAergic 'microcircuit', composed of MSN axon collaterals and GABAergic interneurons. Here, we investigated whether the increased glutamatergic neurotransmission observed after prolonged withdrawal is accompanied by altered GABAergic neurotransmission, focusing on NAc core. Rats self-administered cocaine or saline (6 hours/day) and then underwent >40 days of withdrawal. First, we investigated parvalbumin positive (PV+) interneurons, GABAergic fast-spiking interneurons that regulate MSN activity. Immunohistochemical studies revealed no significant change in PV signal intensity or the number of PV+ cells in cocaine rats versus saline controls. We then screened PV and other interneuron markers using immunoblotting. We detected no changes in levels of PV, calretinin, calbindin or neuronal nitric oxide synthase. Because expression of these markers is activity dependent, our results suggest no marked changes in interneuron activity. Finally, we utilized local field potential recording, which can detect GABA-mediated alterations at the circuit level, to investigate potential changes in two circuits implicated in cocaine craving: prelimbic prefrontal cortex to NAc core and basolateral amygdala to NAc core. We detected differential adaptations in these circuits, some of which may involve GABA. Overall, our results suggest that alterations in GABA transmission may accompany incubation of cocaine craving, but they are circuit specific and less pronounced than alterations in glutamate transmission.
Asunto(s)
Complejo Nuclear Basolateral/fisiopatología , Trastornos Relacionados con Cocaína/fisiopatología , Neuronas GABAérgicas/efectos de los fármacos , Núcleo Accumbens/fisiopatología , Corteza Prefrontal/fisiopatología , Síndrome de Abstinencia a Sustancias/fisiopatología , Animales , Complejo Nuclear Basolateral/efectos de los fármacos , Modelos Animales de Enfermedad , Electroforesis en Gel de Poliacrilamida , Immunoblotting , Inmunohistoquímica , Interneuronas/efectos de los fármacos , Masculino , Núcleo Accumbens/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , AutoadministraciónRESUMEN
Overdose intake of ethanol can impair cerebellar cortical neurons to integrate and transfer external information, resulting in a dysfunction of cerebellar motor regulation or cerebellar ataxia. However, the mechanisms underlying ethanol-impaired transfer of sensory information from cerebellar cortical molecular layer neurons remain unclear. In the present study, we investigated the effects of ethanol on sensory stimulation-evoked responses in the cerebellar molecular layer of urethane-anesthetized mice, by electrophysiological and pharmacological methods. Our results demonstrated that air-puff stimulation (30 ms, 50-60 psi) of the ipsilateral whisker-pad evoked field potential responses in the molecular layer of the cerebellar cortex folium Crus II, which expressed a negative component (N1) followed by a gamma-aminobutyric acid receptor A (GABAA)-mediated positive component (P1). Cerebellar surface perfusion of ethanol between 2 and 5mM did not change the latency of the evoked responses and the amplitude of N1, but enhanced the amplitude and the area under the curve of P1. Interestingly, high concentrations (>20mM) of ethanol induced a significantly decrease in the amplitude and area under the curve of P1. Furthermore, high concentration ethanol (300 mM) significantly decreased the rise in tau and tau decay value of P1, whereas low concentration ethanol (2-5mM) significantly increased these values of P1. Inhibition of GABAA receptor activity reversed P1 and also abolished the effects of ethanol on sensory stimulation-evoked responses. These results indicated that ethanol induced a bidirectional effect on the sensory stimulation-evoked GABAergic responses in the cerebellar cortical molecular layer, suggesting that acute alcohol intake impacted the sensory information processing of cerebellar cortex.