scholarly journals Cocaine memory reactivation induces functional adaptations of fast-spiking interneurons in the rat medial prefrontal cortex

2019 ◽  
Author(s):  
Emily T. Jorgensen ◽  
Angela E. Gonzalez ◽  
John H. Harkness ◽  
Deborah M. Hegarty ◽  
Delta J. Burchi ◽  
...  

AbstractPerineuronal nets (PNNs) are specialized extracellular matrix structures that ensheathe parvalbumin-containing fast-spiking interneurons (PV FSIs) and play a key role in neuroplasticity. We previously showed that PNNs within the prelimbic prefrontal cortex (PL PFC) are required for the maintenance of cocaine-associated memories following cocaine memory reactivation. However, how cocaine memory reactivation affects PNNs, PV, and corresponding changes in PV FSI function are unknown. In this study, we characterized the electrophysiological properties of PV FSIs and corresponding changes in PNN and PV intensity within the PL PFC prior to and after cocaine memory reactivation. Adult male Sprague-Dawley rats were trained to acquire cocaine-conditioned place preference (CPP) and, following cocaine-CPP memory reactivation (30 m, 2 h, and 24 h post-reactivation), we measured PNN intensity (determined by Wisteria floribunda agglutinin [WFA] staining) as well as PV intensity using immunohistochemistry. The intensity of PV staining was reduced at all time points following memory reactivation with no changes in WFA intensity. Using whole-cell electrophysiology we found a reduction in the number of action potentials at 30 m and 2 h that returned to control levels by 24 h. The attenuation in firing was accompanied by a presumed compensatory increase in excitatory synaptic transmission, which was corroborated by an increase in VGluT1 puncta apposing PV/PNN neurons. Collectively, our results indicate that cocaine memory reactivation decreases PV intensity, which may play a role in decreasing excitation of PV FSIs. Thus, the inhibitory tone onto pyramidal neurons may be decreased following memory reactivation, resulting in an increase in PFC output to promote cocaine-seeking behaviors.

2018 ◽  
Vol 33 (1) ◽  
pp. 132-144
Author(s):  
Tracey A Larson ◽  
Casey E O’Neill ◽  
Michaela P Palumbo ◽  
Ryan K Bachtell

Background: Caffeine consumption by children and adolescents has risen dramatically in recent years, yet the lasting effects of caffeine consumption during adolescence remain poorly understood. Aim: These experiments explore the effects of adolescent caffeine consumption on cocaine self-administration and seeking using a rodent model. Methods: Sprague-Dawley rats consumed caffeine for 28 days during the adolescent period. Following the caffeine consumption period, the caffeine solution was replaced with water for the remainder of the experiment. Age-matched control rats received water for the duration of the study. Behavioral testing in a cocaine self-administration procedure occurred during adulthood (postnatal days 62–82) to evaluate how adolescent caffeine exposure influenced the reinforcing properties of cocaine. Cocaine seeking was also tested during extinction training and reinstatement tests following cocaine self-administration. Results: Adolescent caffeine consumption increased the acquisition of cocaine self-administration and increased performance on different schedules of reinforcement. Consumption of caffeine in adult rats did not produce similar enhancements in cocaine self-administration. Adolescent caffeine consumption also produced an upward shift in the U-shaped dose response curve on cocaine self-administration maintained on a within-session dose-response procedure. Adolescent caffeine consumption had no effect on cocaine seeking during extinction training or reinstatement of cocaine seeking by cues or cocaine. Conclusions: These findings suggest that caffeine consumption during adolescence may enhance the reinforcing properties of cocaine, leading to enhanced acquisition that may contribute to increased addiction vulnerability.


Synapse ◽  
2013 ◽  
Vol 68 (3) ◽  
pp. 114-126 ◽  
Author(s):  
Israel Camacho-Abrego ◽  
Gullermina Tellez-Merlo ◽  
Angel I. Melo ◽  
Antonio Rodríguez-Moreno ◽  
Linda Garcés ◽  
...  

2011 ◽  
Vol 26 (S2) ◽  
pp. 652-652
Author(s):  
N. Ladurelle ◽  
C. Potard ◽  
C. Gabriel-Gracia ◽  
E. Mocaër ◽  
E. Beaulieu ◽  
...  

Neuronal plasticity alterations including cytoskeletal dynamics and synaptic markers have been recently associated with the treatment of major depression. Here we investigated the effects of agomelatine, a novel antidepressant with melatonergic (MT1/MT2) agonist and 5-HT2C receptor antagonist properties, on cytoskeletal microtubular proteins and synaptic markers in the rat hippocampus, prefrontal cortex (PFC) and amygdala.Adult male Sprague Dawley rats received daily i.p. administration of hydroxyethylcellulose 1% (vehicle) or agomelatine (40mg/kg) for 22 days. The rats were then sacrificed and hippocampi, PFC and amygdala dissected for analyses of microtubule dynamics markers (Tyr/Glu-Tub, Delta2-Tub and Acet-Tub) and synaptic markers (synaptophysin, PSD-95 and spinophilin) by Western blot.In the PFC, agomelatine decreased Tyr/Glu-Tub and the neuronal-specific Delta2-Tub, suggesting decreased microtubule dynamics. In contrast, in the hippocampus Tyr/Glu-Tub and Delta2-Tub were increased, indicative of enhanced microtubule dynamics. A similar pattern to those seen in the hippocampus, but of higher magnitude, was observed in the amygdala where an important increase of Tyr/Glu-Tub accompanied by a decrease of the stable form Acet-Tub was observed. These findings were paralleled by decreased hippocampal spinophilin (dendritic spines marker), increased synaptophysin (pre-synaptic marker) and spinophilin in the PFC and amygdala and increased PSD-95 (post-synaptic marker) in the amygdala, all consistent with synaptic remodelling phenomena.Taken together, these data shown that chronic agomelatine induces a differential modulation of microtubule dynamics and synaptic markers in the rat hippocampus, PFC and amygdala. These findings may have a particular relevance considering the fundamental role of these three brain areas in depression.


2005 ◽  
Vol 94 (5) ◽  
pp. 3009-3022 ◽  
Author(s):  
Leonid S. Krimer ◽  
Aleksey V. Zaitsev ◽  
Gabriela Czanner ◽  
Sven Kröner ◽  
Guillermo González-Burgos ◽  
...  

In primates, little is known about intrinsic electrophysiological properties of neocortical neurons and their morphological correlates. To classify inhibitory cells (interneurons) in layers 2–3 of monkey dorsolateral prefrontal cortex we used whole cell voltage recordings and intracellular labeling in slice preparation with subsequent morphological reconstructions. Regular spiking pyramidal cells have been also included in the sample. Neurons were successfully segregated into three physiological clusters: regular-, intermediate-, and fast-spiking cells using cluster analysis as a multivariate exploratory technique. When morphological types of neurons were mapped on the physiological clusters, the cluster of regular spiking cells contained all pyramidal cells, whereas the intermediate- and fast-spiking clusters consisted exclusively of interneurons. The cluster of fast-spiking cells contained all of the chandelier cells and the majority of local, medium, and wide arbor (basket) interneurons. The cluster of intermediate spiking cells predominantly consisted of cells with the morphology of neurogliaform or vertically oriented (double-bouquet) interneurons. Thus a quantitative approach enabled us to demonstrate that intrinsic electrophysiological properties of neurons in the monkey prefrontal cortex define distinct cell types, which also display distinct morphologies.


2019 ◽  
Vol 33 (2) ◽  
pp. 230-243 ◽  
Author(s):  
Samuel J Millard ◽  
Jeremy S Lum ◽  
Francesca Fernandez ◽  
Katrina Weston-Green ◽  
Kelly A Newell

Background: With approximately 10% of pregnant women prescribed antidepressant drugs for the treatment of depressive disorders, there is growing concern regarding the potential long-term effects of this exposure on offspring. Research is needed in clinically relevant models to determine the effects on offspring behaviour and associated neurobiological systems. Aim: The aim of this study was to determine the effects of maternal fluoxetine treatment on anxiety-like and depressive-like behaviours in adolescent offspring as well as associated glutamatergic markers, using a clinically relevant rodent model of depression. Methods: Wistar-Kyoto (model of innate depression) and Sprague-Dawley rats were treated with fluoxetine (10 mg/kg) from gestational day 0 to postnatal day 14. Male offspring underwent behavioural testing (open field, elevated plus maze, forced swim test) at adolescence followed by quantitative immuno-detection of glutamatergic markers in the prefrontal cortex and ventral hippocampus. Results: Perinatal fluoxetine exposure exacerbated the anxiety-like and depressive-like phenotype in Wistar-Kyoto offspring and induced an anxiety-like and depressive-like phenotype in Sprague-Dawley offspring. Wistar-Kyoto offspring showed reductions in NMDA receptor NR1, NR2A and NR2B subunits, as well as post-synaptic density 95 (PSD-95) and metabotropic glutamate receptor subtype 1 (mGluR1) in the prefrontal cortex; perinatal fluoxetine exposure further reduced NR1, NR2A, PSD-95 and mGluR1 expression in Wistar-Kyoto as well as Sprague-Dawley offspring. In the ventral hippocampus perinatal fluoxetine exposure reduced PSD-95 and increased metabotropic glutamate receptor subtype 5 (mGluR5) and Homer1b/c in both Sprague-Dawley and Wistar-Kyoto strains. Conclusion: These findings suggest that maternal fluoxetine treatment exacerbates effects of underlying maternal depression on offspring behaviour, which may be mediated through alterations in the glutamatergic system. Further research investigating how to minimise these effects, whilst ensuring optimal treatment for mothers, is essential to move the field forward.


2020 ◽  
Vol 10 (4) ◽  
pp. 221
Author(s):  
Gustavo Hernández-Carballo ◽  
Evelyn A. Ruíz-Luna ◽  
Gustavo López-López ◽  
Elias Manjarrez ◽  
Jorge Flores-Hernández

Changes in stimuli and feeding in pregnant mothers alter the behavior of offspring. Since behavior is mediated by brain activity, it is expected that postnatal changes occur at the level of currents, receptors or soma and dendrites structure and modulation. In this work, we explore at the mechanism level the effects on Sprague–Dawley rat offspring following the administration of serotonin (5-HT) agonist 5-methoxytryptamine (5-MT). We analyzed whether 5-HT affects the glutamate-activated (IGlut) and N-methyl-D-aspartate (NMDA)-activated currents (IGlut, INMDA) in dissociated pyramidal neurons from the prefrontal cortex (PFC). For this purpose, we performed voltage-clamp experiments on pyramidal neurons from layers V-VI of the PFC of 40-day-old offspring born from 5-MT-treated mothers at the gestational days (GD) 11 to 21. We found that the pyramidal-neurons from the PFC of offspring of mothers treated with 5-MT exhibit a significant increased reduction in both the IGlut and INMDA when 5-HT was administered. Our results suggest that the concentration increase of a neuromodulator during the gestation induces changes in its modulatory action over the offspring ionic currents during the adulthood thus contributing to possible psychiatric disorders.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Fang-hao Zheng ◽  
Ping Wei ◽  
Hui-ling Huo ◽  
Xue-feng Xing ◽  
Fei-long Chen ◽  
...  

Herb Ephedra(Ma Huang in Chinese) andRamulus Cinnamomi(Gui Zhi in Chinese) are traditional Chinese herbs, often used together to treat asthma, nose and lung congestion, and fever with anhidrosis. Due to the adverse effects of ephedrine, clinical use of Ma Huang is restricted. However, Gui Zhi extract has been reported to decrease spontaneous activity in rats and exert anti-inflammatory and neuroprotective effects. The present study explored the possible inhibitory effect of Gui Zhi on Ma Huang-induced neurotoxicity in rats when the two herbs were used in combination. All Ma Huang and Ma Huang-Gui Zhi herb pair extracts were prepared using methods of traditional Chinese medicine and were normalized based on the ephedrine content. Two-month-old male Sprague-Dawley rats (n=6rats/group) were administered Ma Huang or the Ma Huang-Gui Zhi herb pair extracts for 7 days (ephedrine = 48 mg/kg), and locomotor activity was measured. After 7 days, oxidative damage in the prefrontal cortex was measured. Gui Zhi decreased hyperactivity and sensitization produced by repeated Ma Huang administration and attenuated oxidative stress induced by Ma Huang. The results of this study demonstrate the neuroprotective potential of Gui Zhi in Ma Huang-induced hyperactivity and oxidative damage in the prefrontal cortex of rats when used in combination.


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