Asunto(s)
Cocaína , Integrina beta3 , Señales (Psicología) , Matriz Extracelular , Humanos , Plasticidad Neuronal , RecurrenciaRESUMEN
We previously reported that perineuronal nets (PNNs) are required for cocaine-associated memories. Perineuronal nets are extracellular matrix that primarily surrounds parvalbumin (PV)-containing, GABAergic fast-spiking interneurons (FSIs) in the medial prefrontal cortex (mPFC). Here we measured the impact of acute (1 d) or repeated (5 d) cocaine exposure on PNNs and PV cells within the prelimbic and infralimbic regions of the mPFC. Adult rats were exposed to 1 or 5 d of cocaine and stained for PNNs (using Wisteria floribunda agglutinin) and PV intensity 2 or 24 h later. In the prelimbic and infralimbic PFC, PNN staining intensity decreased 2 h after 1 d of cocaine exposure but increased after 5 d of cocaine exposure. Cocaine also produced changes in PV intensity, which generally lagged behind that of PNNs. In the prelimbic PFC, both 1 and 5 d of cocaine exposure increased GAD65/67 puncta near PNN-surrounded PV cells, with an increase in the GAD65/67-to-VGluT1 puncta ratio after 5 d of cocaine exposure. In the prelimbic PFC, slice electrophysiology studies in FSIs surrounded by PNNs revealed that both 1 and 5 d of cocaine exposure reduced the number of action potentials 2 h later. Synaptic changes demonstrated that 5 d of cocaine exposure increased the inhibition of FSIs, potentially reducing the inhibition of pyramidal neurons and contributing to their hyperexcitability during relapse behavior. These early and rapid responses to cocaine may alter the network stability of PV FSIs that partially mediate the persistent and chronic nature of drug addiction.
Asunto(s)
Cocaína/farmacología , Interneuronas/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Sinapsis/efectos de los fármacos , Animales , Matriz Extracelular/metabolismo , Masculino , Red Nerviosa/efectos de los fármacos , Red Nerviosa/fisiología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Parvalbúminas/metabolismo , Ratas Sprague-DawleyRESUMEN
Traumatic brain injury (TBI) commonly results in cognitive and psychiatric problems. Cognitive impairments occur in approximately 30% of patients suffering from mild TBI (mTBI), and correlational evidence from clinical studies indicates that substance abuse may be increased following mTBI. However, understanding the lasting cognitive and psychiatric problems stemming from mTBI is difficult in clinical settings where pre-injury assessment may not be possible or accurate. Therefore, we used a previously characterized blast model of mTBI (bTBI) to examine cognitive- and addiction-related outcomes. We previously demonstrated that this model leads to bilateral damage of the medial prefrontal cortex (mPFC), a region critical for cognitive function and addiction. Rats were exposed to bTBI and tested in operant learning tasks several weeks after injury. bTBI rats made more errors during acquisition of a cue discrimination task compared to sham treated rats. Surprisingly, we observed no differences between groups in set shifting and delayed matching to sample, tasks known to require the mPFC. Separate rats performed cocaine self-administration. No group differences were found in intake or extinction, and only subtle differences were observed in drug-primed reinstatement 3-4 months after injury. These findings indicate that bTBI impairs acquisition of a visual discrimination task and that bTBI does not significantly increase the ability of cocaine exposure to trigger drug seeking.
Asunto(s)
Traumatismos por Explosión/psicología , Conmoción Encefálica/psicología , Disfunción Cognitiva/etiología , Comportamiento de Búsqueda de Drogas , Percepción Visual , Animales , Traumatismos por Explosión/complicaciones , Traumatismos por Explosión/fisiopatología , Conmoción Encefálica/complicaciones , Conmoción Encefálica/fisiopatología , Cocaína , Modelos Animales de Enfermedad , Masculino , Corteza Prefrontal/fisiopatología , Ratas , Ratas Sprague-Dawley , AutoadministraciónRESUMEN
Perineuronal nets (PNNs) are aggregations of extracellular matrix molecules that are critical for plasticity. Their altered development or changes during adulthood appear to contribute to a wide range of diseases/disorders of the brain. An increasing number of studies examining the contribution of PNN to various behaviors and types of plasticity have analyzed the fluorescence intensity of Wisteria floribunda agglutinin (WFA) as an indirect measure of the maturity of PNNs, with brighter WFA staining corresponding to a more mature PNN and dim WFA staining corresponding to an immature PNN. However, a clearly-defined and unified method for assessing the intensity of PNNs is critical to allow us to make comparisons across studies and to advance our understanding of how PNN plasticity contributes to normal brain function and brain disease states. Here we examined methods of PNN intensity quantification and demonstrate that creating a region of interest around each PNN and subtracting appropriate background is a viable method for PNN intensity quantification that can be automated. This method produces less variability and bias across experiments compared to other published analyses, and this method increases reproducibility and reliability of PNN intensity measures, which is critical for comparisons across studies in this emerging field.