mPFC Of Rats Research Articles

DUSP1 Promotes Microglial Polarization toward M2 Phenotype in the Medial Prefrontal Cortex of Neuropathic Pain Rats via Inhibition of MAPK Pathway.

Shifting microglial polarization from M1 toward M2 phenotype represents a promising therapeutic strategy for neuropathic pain (NP). Dual-specificity phosphatase-1 (DUSP1) is a key component in regulating anti-inflammatory response. The medial prefrontal cortex (mPFC) is implicated in emotional disorders associated with NP and constitutes a neuroanatomical substrate for exploring mechanisms underlying NP. This study aims to investigate whether DUSP1 regulates microglial M1/M2 polarization in the mPFC in a rat model of NP. Rat model of NP was established by chronic constriction injury (CCI) of the rat sciatic nerve. Lipopolysaccharide (LPS) was used to activate HAPI rat microglial cells as an in vitro inflammatory model. CCI-induced decreased pain threshold, increased cell apoptosis in mPFC, elevated pro-inflammatory M1/M2 microglia ratio, and activated MAPK signaling in the mPFC of rats. Importantly, intra-mPFC injection of DUSP1-expressing lentivirus counteracted these abnormalities. In vitro assay further confirmed that DUSP1 overexpression switched microglial M1 to M2 polarization through inhibition of MAPK signaling activation. DUSP1 switched microglial M1 to M2 polarization in the mPFC and attenuated CCI-induced NP by inhibiting the MAPK signaling.

A Search for Biomarkers of Early-life Stress-related Psychopathology: Focus on 70-kDa Heat Shock Proteins

Clinical studies clearly indicate that early-life stress (ELS) may cause physical and mental health problems later in life. Therefore, the identification of universal biomarkers of ELS-related diseases is very important. The 70-kDa heat shock proteins (HSP70s), specifically HSPA5 and HSPA1B, have been recently shown to be potentially associated with occurrence of anxiety, mood disorders, and schizophrenia; thus, we hypothesized that HSP70s are potential candidate biomarkers of ELS-induced psychopathologies. A maternal separation (MS) procedure in rats was used to model ELS, and the expression of HSPA5 and HSPA1B was investigated in the blood, medial prefrontal cortex (mPFC), and hippocampus of juvenile, preadolescent, and adult animals. We also studied the effects of MS on the long-term potentiation (LTP) and behavioral phenotypes of adult rats. We found that MS enhanced the expression of HSPA1B mRNA in the blood and mPFC of juvenile and preadolescent rats. This increase was accompanied by an increase in the HSPA1A/1B protein levels in the mPFC and hippocampus of juvenile rats that persisted in the mPFC until adulthood. MS juvenile and adult rats showed enhanced HSPA5 mRNA expression in the blood and increased HSPA5 protein expression in the mPFC (juveniles) and hippocampus (adults). Concurrently, MS adult rats exhibited aberrations in LTP in the mPFC and hippocampus and a less anxious behavioral phenotype. These results indicate that MS may produce enduring overexpression of HSPA1B and HSPA5 in the brain and blood. Therefore, both HSP70 family members may be potential candidate peripheral and brain biomarkers of ELS-induced changes in brain functioning.

Coordinated Prefrontal State Transition Leads Extinction of Reward-Seeking Behaviors

Extinction learning suppresses conditioned reward responses and is thus fundamental to adapt to changing environmental demands and to control excessive reward seeking. The medial prefrontal cortex (mPFC) monitors and controls conditioned reward responses. Abrupt transitions in mPFC activity anticipate changes in conditioned responses to altered contingencies. It remains, however, unknown whether such transitions are driven by the extinction of old behavioral strategies or by the acquisition of new competing ones. Using in vivo multiple single-unit recordings of mPFC in male rats, we studied the relationship between single-unit and population dynamics during extinction learning, using alcohol as a positive reinforcer in an operant conditioning paradigm. To examine the fine temporal relation between neural activity and behavior, we developed a novel behavioral model that allowed us to identify the number, onset, and duration of extinction-learning episodes in the behavior of each animal. We found that single-unit responses to conditioned stimuli changed even under stable experimental conditions and behavior. However, when behavioral responses to task contingencies had to be updated, unit-specific modulations became coordinated across the whole population, pushing the network into a new stable attractor state. Thus, extinction learning is not associated with suppressed mPFC responses to conditioned stimuli, but is anticipated by single-unit coordination into population-wide transitions of the internal state of the animal.SIGNIFICANCE STATEMENT The ability to suppress conditioned behaviors when no longer beneficial is fundamental for the survival of any organism. While pharmacological and optogenetic interventions have shown a critical involvement of the mPFC in the suppression of conditioned responses, the neural dynamics underlying such a process are still largely unknown. Combining novel analysis tools to describe behavior, single-neuron response, and population activity, we found that widespread changes in neuronal firing temporally coordinate across the whole mPFC population in anticipation of behavioral extinction. This coordination leads to a global transition in the internal state of the network, driving extinction of conditioned behavior.

Repeated fluoxetine treatment induces transient and long-term astrocytic plasticity in the medial prefrontal cortex of normal adult rats

Fluoxetine (Flx)-induced neuronal plasticity plays an important role in the effective treatment of depression and mood disorders. It is less understood whether repeated Flx treatment induces astrocytic plasticity that outlasts the presence of the drug in the body. We showed previously that Flx-induced neuronal plasticity in the medial prefrontal cortex (mPFC) persisted up to 20 days after the treatment. In this study, adult rats were subjected to a 15-day repeated Flx treatment at a daily dose of 20 mg/kg body weight. Astrocytic metabolites and markers were assessed in the mPFC at day 1 (d1) and day 20 (d20) after the treatment. Significant transient reductions in the concentrations of astrocytic metabolites taurine and myo-inositol and the expressions of glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP4) were observed in the mPFC of Flx-treated rats at d1, which recovered to the control levels at d20. Further, Flx treatment resulted in long-lasting changes in Kir4.1 expression in the mPFC, which remained downregulated at d20. The expression of 5-HT1A receptor in the mPFC of Flx-treated rats was downregulated at d1 but became upregulated at d20. In summary, repeated Flx treatment induces both transient and long-term astrocytic plasticity in the mPFC of adult rats. The changes observed at d1 are consistent with disturbed water homeostasis and astrocytic de-maturation in the mPFC. The persistent changes in the expressions of Kir4.1 and 5-HT1A at d20, presumably of the astrocytic origin, might have contributed to the long-term neurotrophic effects of repeated Flx treatment in the mPFC.

Choice-dependent cross-modal interaction in the medial prefrontal cortex of rats

Cross-modal interaction (CMI) could significantly influence the perceptional or decision-making process in many circumstances. However, it remains poorly understood what integrative strategies are employed by the brain to deal with different task contexts. To explore it, we examined neural activities of the medial prefrontal cortex (mPFC) of rats performing cue-guided two-alternative forced-choice tasks. In a task requiring rats to discriminate stimuli based on auditory cue, the simultaneous presentation of an uninformative visual cue substantially strengthened mPFC neurons' capability of auditory discrimination mainly through enhancing the response to the preferred cue. Doing this also increased the number of neurons revealing a cue preference. If the task was changed slightly and a visual cue, like the auditory, denoted a specific behavioral direction, mPFC neurons frequently showed a different CMI pattern with an effect of cross-modal enhancement best evoked in information-congruent multisensory trials. In a choice free task, however, the majority of neurons failed to show a cross-modal enhancement effect and cue preference. These results indicate that CMI at the neuronal level is context-dependent in a way that differs from what has been shown in previous studies.

Microinjection of the BDNF receptor antagonist ANA-12 into the nucleus accumbens and medial-prefrontal cortex attenuates morphine-induced reward memory, and alterations of BDNF levels and apoptotic cells in rats

This study was designed to examine the effects of intra- nucleus accumbens (NAc) of BDNF receptor antagonist ANA-12 on the acquisition and expression and intra- medial-prefrontal cortex (mPFC) of ANA-12 on the extinction and reinstatement of morphine-induced conditioned place preference (CPP) and also BDNF levels and apoptotic neurons in the NAc and mPFC of rats. In this study, adult male Wistar rats (200–250 g) were used. Two separate cannulas were inserted bilaterally into the NAc and/or mPFC. ANA-12 (3 μg/0.5 μl/side) was injected into the NAc and/or mPFC to evaluate the rewarding effects of morphine using a CPP paradigm. Then, the levels of BDNF and apoptotic in the NAc and mPFC were assessed at the end of each treatment phase using ELISA and TUNEL methods, respectively. All of vehicle-treated rats following morphine CPP showed the increase of BDNF levels and apoptotic neurons in the NAc and mPFC. ANA-12 significantly attenuated the acquisition and expression of morphine-induced CPP, BDNF levels and apoptotic neurons in the NAc during the acquisition, but not the expression phase. Also, ANA-12 significantly facilitated the extinction, but no effect on reinstatement of morphine CPP, and decreased BDNF levels and apoptotic neurons in the mPFC during the extinction, but not the reinstatement. We conclude that blocking TrkB with ANA-12 showed therapeutic effects on morphine-associated reward memory and neuronal death in the NAc and mPFC induced by morphine CPP. Thus, the BDNF–TrkB signaling may be important in the acquisition, expression, extinction, but not the reinstatement of morphine CPP.

Reduced Information Transmission of Medial Prefrontal Cortex to Basolateral Amygdala Inhibits Exploratory Behavior in Depressed Rats.

Depression is a mental and neurological disease that reduces the desire for exploration. Dysregulation of the information transmission between medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) is associated with depression. However, which direction of information transmission (mPFC-BLA or BLA-mPFC) related to the decline of exploratory interests in depression is unclear. Therefore, it is important to determine what specific changes occur in mPFC and BLA information transmission in depressed rats during exploratory behavior. In the present study, local field potentials (LFPs) were recorded via multi-electrodes implanted in the mPFC and BLA for the control and depression groups of rats when they were exploring in an open field. The theta band was determined to be the characteristic band of exploratory behavior. The direct transfer function (DTF) was used to calculate the mPFC and BLA bidirectional information flow (IF) to measure information transmission. Compared with the control group, the theta IF of mPFC-BLA in the depression group was significantly reduced, and there was no significant difference in theta IF of BLA-mPFC between the two groups. Our results indicated that the reduction of mPFC-BLA information transmission can inhibit the exploratory behavior of depressed rats.

Abstinence from ethanol dependence produces concomitant cortical gray matter abnormalities, microstructural deficits and cognitive dysfunction

Previous studies demonstrate that ethanol dependence induced by repeating cycles of chronic intermittent ethanol vapor exposure (CIE) followed by protracted abstinence (CIE-PA) produces significant alterations in oligodendrogenesis in the rodent medial prefrontal cortex (mPFC). Specifically, CIE-PA produced an unprecedented increase in premyelinating oligodendroglial progenitor cells and myelin, which have been associated with persistent elevated drinking behaviors during abstinence. The current study used neuroimaging and electron microscopy to evaluate the integrity of enhanced myelin and microstructural deficits underlying enhanced myelination in the mPFC in male rats experiencing forced abstinence for 1 day (D), 7D, 21D and 42D following seven weeks of CIE. In vivo diffusion tensor imaging (DTI) detected altered microstructural integrity in the mPFC and corpus callosum (CC). Altered integrity was characterized as reduced fractional anisotropy (FA) in the CC, and enhanced mean diffusivity (MD) in the mPFC in 7D abstinent rats. Increased MD occurred concomitantly with increases in myelin associated proteins, flayed myelin and enhanced mitochondrial stress in the mPFC in 7D abstinent rats, suggesting that the increases in myelination during abstinence was aberrant. Evaluation of cognitive performance via Pavlovian conditioning in 7D abstinent rats revealed reduced retrieval and recall of fear memories dependent on the mPFC. These findings indicate that forced abstinence from moderate to severe alcohol use disorder produces gray matter damage via myelin dysfunction in the mPFC and that these microstructural changes were associated with deficits in PFC dependent behaviors.

Altered synaptic ultrastructure in the prefrontal cortex of Shank3-deficient rats

BackgroundDeletion or mutations of SHANK3 lead to Phelan–McDermid syndrome and monogenic forms of autism spectrum disorder (ASD). SHANK3 encodes its eponymous scaffolding protein at excitatory glutamatergic synapses. Altered morphology of dendrites and spines in the hippocampus, cerebellum, and striatum have been associated with behavioral impairments in Shank3-deficient animal models. Given the attentional deficit in these animals, our study explored whether deficiency of Shank3 in a rat model alters neuron morphology and synaptic ultrastructure in the medial prefrontal cortex (mPFC).MethodsWe assessed dendrite and spine morphology and spine density in mPFC layer III neurons in Shank3-homozygous knockout (Shank3-KO), heterozygous (Shank3-Het), and wild-type (WT) rats. We used electron microscopy to determine the density of asymmetric synapses in mPFC layer III excitatory neurons in these rats. We measured postsynaptic density (PSD) length, PSD area, and head diameter (HD) of spines at these synapses.ResultsBasal dendritic morphology was similar among the three genotypes. Spine density and morphology were comparable, but more thin and mushroom spines had larger head volumes in Shank3-Het compared to WT and Shank3-KO. All three groups had comparable synapse density and PSD length. Spine HD of total and non-perforated synapses in Shank3-Het rats, but not Shank3-KO rats, was significantly larger than in WT rats. The total and non-perforated PSD area was significantly larger in Shank3-Het rats compared to Shank3-KO rats. These findings represent preliminary evidence for synaptic ultrastructural alterations in the mPFC of rats that lack one copy of Shank3 and mimic the heterozygous loss of SHANK3 in Phelan–McDermid syndrome.LimitationsThe Shank3 deletion in the rat model we used does not affect all isoforms of the protein and would only model the effect of mutations resulting in loss of the N-terminus of the protein. Given the higher prevalence of ASD in males, the ultrastructural study focused only on synaptic structure in male Shank3-deficient rats.ConclusionsWe observed increased HD and PSD area in Shank3-Het rats. These observations suggest the occurrence of altered synaptic ultrastructure in this animal model, further pointing to a key role of defective expression of the Shank3 protein in ASD and Phelan–McDermid syndrome.

Active maintenance of eligibility trace in rodent prefrontal cortex

Even though persistent neural activity has been proposed as a mechanism for maintaining eligibility trace, direct empirical evidence for active maintenance of eligibility trace has been lacking. We recorded neuronal activity in the medial prefrontal cortex (mPFC) in rats performing a dynamic foraging task in which a choice must be remembered until its outcome on the timescale of seconds for correct credit assignment. We found that mPFC neurons maintain significant choice signals during the time period between action selection and choice outcome. We also found that neural signals for choice, outcome, and action value converge in the mPFC when choice outcome was revealed. Our results indicate that the mPFC maintains choice signals necessary for temporal credit assignment in the form of persistent neural activity in our task. They also suggest that the mPFC might update action value by combining actively maintained eligibility trace with action value and outcome signals.

Cell Assemblies in the Cortico-Hippocampal-Reuniens Network during Slow Oscillations.

The nucleus reuniens (NR) is an important anatomic and functional relay between the medial prefrontal cortex (mPFC) and the hippocampus (HPC). Whether the NR controls neuronal assemblies, a hallmark of information exchange between the HPC and mPFC for memory transfer/consolidation, is not known. Using simultaneous local field potential and unit recordings in NR, HPC, and mPFC in male rats during slow oscillations under anesthesia, we identified a reliable sequential activation of NR neurons at the beginning of UP states, which preceded mPFC ones. NR sequences were spatially organized, from dorsal to ventral NR. Chemical inactivation of the NR disrupted mPFC sequences at the onset of UP states as well as HPC sequences present during sharp-wave ripples. We conclude that the NR contributes to the coordination and stabilization of mPFC and HPC neuronal sequences during slow oscillations, possibly via the early activation of its own sequences.SIGNIFICANCE STATEMENT Neuronal assemblies are believed to be instrumental to code/encode/store information. They can be recorded in different brain regions, suggesting that widely distributed networks of networks are involved in such information processing. The medial prefrontal cortex, the hippocampus, and the thalamic nucleus reuniens constitute a typical example of a complex network involved in memory consolidation. In this study, we show that spatially organized cells assemblies are recruited in the nucleus reuniens at the UP state onset during slow oscillations. Nucleus reuniens activity appears to be necessary to the stability of medial prefrontal cortex and hippocampal cell assembly formation during slow oscillations. This result further highlights the role of the nucleus reuniens as a functional hub for exchanging and processing memories.

Noradrenergic Source of Dopamine Assessed by Microdialysis in the Medial Prefrontal Cortex.

Previous results indicate that dopamine (DA) release in the medial prefrontal cortex (mPFC) is modified by α2 adrenoceptor- but not D2 DA receptor- agonists and antagonists, suggesting that DA measured by microdialysis in the mPFC originates from noradrenergic terminals. Accordingly, noradrenergic denervation was found to prevent α2-receptor-mediated rise and fall of extracellular DA induced by atipamezole and clonidine, respectively, in the mPFC. The present study was aimed to determine whether DA released by dopaminergic terminals in the mPFC is not detected by in vivo microdialysis because is readily taken up by norepinephrine transporter (NET). Accordingly, the D2-antagonist raclopride increased the electrical activity of DA neurons in the ventral tegmental area (VTA) and enhanced extracellular DOPAC but failed to modify DA in the mPFC. However, in rats whose NET was either inactivated by nisoxetine or eliminated by noradrenergic denervation, raclopride still elevated extracellular DOPAC and activated dopaminergic activity, but also increased DA. Conversely, the D2-receptor agonist quinpirole reduced DOPAC but failed to modify DA in the mPFC in control rats. However, in rats whose NET was eliminated by noradrenergic denervation or inhibited by locally perfused nisoxetine, quinpirole maintained its ability to reduce DOPAC but acquired that of reducing DA. Moreover, raclopride and quinpirole, when locally perfused into the mPFC of rats subjected to noradrenergic denervation, were able to increase and decrease, respectively, extracellular DA levels, while being ineffective in control rats. Transient inactivation of noradrenergic neurons by clonidine infusion into the locus coeruleus, a condition where NET is preserved, was found to reduce extracellular NE and DA in the mPFC, whereas noradrenergic denervation, a condition where NET is eliminated, almost totally depleted extracellular NE but increased DA. Both transient inactivation and denervation of noradrenergic neurons were found to reduce the number of spontaneously active DA neurons and their bursting activity in the VTA. The results indicate that DA released in the mPFC by dopaminergic terminals is not detected by microdialysis unless DA clearance from extracellular space is inactivated. They support the hypothesis that noradrenergic terminals are the main source of DA measured by microdialysis in the mPFC during physiologically relevant activities.

Inhibition of the fatty acid amide hydrolase changes behaviors and brain catecholamines in a sex-specific manner in rats exposed to chronic unpredictable stress

Sex differences in the susceptibility to chronic unpredictable stress (CUS) and the effects of fatty acid amide hydrolase (FAAH) inhibitor URB597 in rats have been investigated in this study. In this context, we investigated the effects of prolonged treatment with URB597 on behavior, pro-inflammatory interleukin-6 (IL-6) and anti-inflammatory interleukin-10 (IL-10), catecholamine content and the expression of its biosynthetic and degrading enzymes in the hippocampus, hypothalamus and medial prefrontal cortex (mPFC) of rats subjected to CUS. The results show that CUS increases anxiety-like and depression-like behaviors but it was more pronounced in females. The data suggests sex differences in brain cytokines, catecholamines and their enzymes of synthesis and degradation expression in response to CUS. Our findings indicate that the FAAH inhibitor URB597 differently regulated catecholamine levels and its enzymes of synthesis and degradation in the examined brain areas of male and female rats. URB treatment failed to reduce anxiety or restore reduced norepinephrine and did not affect enzymes of catecholamine degradation in the mPFC, hippocampus and hypothalamus of CUS female rats. These studies are important because they investigate the neurochemical consequences of stress related mood disorders that might lead to the development of sex specific treatments.

Representations of On-Going Behavior and Future Actions During a Spatial Working Memory Task by a High Firing-Rate Population of Medial Prefrontal Cortex Neurons.

Spatial working memory (SWM) requires the encoding, maintenance, and retrieval of spatially relevant information to guide decision-making. The medial prefrontal cortex (mPFC) has long been implicated in the ability of rodents to perform SWM tasks. While past studies have demonstrated that mPFC ensembles reflect past and future experiences, most findings are derived from tasks that have an experimental overlap between the encoding and retrieval of trajectory specific information. In this study, we recorded single units from the mPFC of rats as they performed a T-maze delayed non-match to position (DNMP) task. This task consists of an encoding dominant sample phase, a memory maintenance delay period, and retrieval dominant choice phase. Using a linear classifier, we investigated whether distinct ensembles collectively reflect various trajectory-dependent experiences. We find that a population of high-firing rate mPFC neurons both predict a future choice and reflect changes in trajectory-dependent behaviors. We then developed a modeling procedure that estimated the number of high and low-firing rate units required to dissociate between various experiences. We find that low firing rate ensembles weakly reflect the direction that rats were forced to turn on the sample phase. This was in contrast to the highly active population that could effectively predict both future decision-making on early stem traversals and trajectory-divergences at T-junction. Finally, we compared the ensemble size necessary to code a forced trajectory to the size required to predict a decision. We provide evidence to suggest that a larger number of highly active neurons are employed during decision-making processes when compared to rewarded forced behaviors. Together, our study provides important insight into how specific ensembles of mPFC units support upcoming choices and ongoing behavior during SWM.

Layer-Specific Inhibitory Microcircuits of Layer 6 Interneurons in Rat Prefrontal Cortex.

GABAergic interneurons in different cortical areas play important roles in diverse higher-order cognitive functions. The heterogeneity of interneurons is well characterized in different sensory cortices, in particular in primary somatosensory and visual cortex. However, the structural and functional properties of the medial prefrontal cortex (mPFC) interneurons have received less attention. In this study, a cluster analysis based on axonal projection patterns revealed four distinct clusters of L6 interneurons in rat mPFC: Cluster 1 interneurons showed axonal projections similar to Martinotti-like cells extending to layer 1, cluster 2 displayed translaminar projections mostly to layer 5, and cluster 3 interneuron axons were confined to the layer 6, whereas those of cluster 4 interneurons extend also into the white matter. Correlations were found between neuron location and axonal distribution in all clusters. Moreover, all cluster 1 L6 interneurons showed a monotonically adapting firing pattern with an initial high-frequency burst. All cluster 2 interneurons were fast-spiking, while neurons in cluster 3 and 4 showed heterogeneous firing patterns. Our data suggest that L6 interneurons that have distinct morphological and physiological characteristics are likely to innervate different targets in mPFC and thus play differential roles in the L6 microcircuitry and in mPFC-associated functions.

Morinda officinalis oligosaccharides ameliorate depressive-like behaviors in poststroke rats through upregulating GLUT3 to improve synaptic activity.

Poststroke depression (PSD) is one of the most common psychiatric diseases afflicting stroke survivors, yet the underlying mechanism is poorly understood. The pathophysiology of PSD is presumably multifactorial, involving ischemia-induced disturbance in the context of psychosocial distress. The homeostasis of glucose metabolism is crucial to neural activity. In this study, we showed that glucose consumption was decreased in the medial prefrontal cortex (mPFC) of PSD rats. The suppressed glucose metabolism was due to decreased glucose transporter-3 (GLUT3) expression, the most abundant and specific glucose transporter of neurons. We also found Morinda officinalis oligosaccharides (MOOs), approved as an antidepressive Chinese medicine, through upregulating GLUT3 expression in the mPFC, improved glucose metabolism, and enhanced synaptic activity, which ultimately ameliorated depressive-like behavior in PSD rats. We further confirmed the mechanism that MOOs induce GLUT3 expression via the PKA/pCREB pathway in PSD rats. Our work showed that MOOs treatment is capable of restoring GLUT3 level to improve depressive-like behaviors in PSD rats. We also propose GLUT3 as a potential therapeutic target for PSD and emphasize the importance of metabolism disturbance in PSD pathology.

Adolescent chronic intermittent toluene inhalation dynamically regulates the transcriptome and neuronal methylome within the rat medial prefrontal cortex.

Inhalants containing the volatile solvent toluene are misused to induce euphoria or intoxication. Inhalant abuse is most common during adolescence and can result in cognitive impairments during an important maturational period. Despite evidence suggesting that epigenetic modifications may underpin the cognitive effects of inhalants, no studies to date have thoroughly investigated toluene-induced regulation of the transcriptome or discrete epigenetic modifications within the brain. To address this, we investigated effects of adolescent chronic intermittent toluene (CIT) inhalation on gene expression and DNA methylation profiles within the rat medial prefrontal cortex (mPFC), which undergoes maturation throughout adolescence and has been implicated in toluene-induced cognitive deficits. Employing both RNA-seq and genome-wide Methyl CpG Binding Domain (MBD) Ultra-seq analysis, we demonstrate that adolescent CIT inhalation (10 000 ppm for 1 h/day, 3 days/week for 4 weeks) induces both transient and persistent changes to the transcriptome and DNA methylome within the rat mPFC for at least 2 weeks following toluene exposure. We demonstrate for the first time that adolescent CIT exposure results in dynamic regulation of the mPFC transcriptome likely relating to acute inflammatory responses and persistent deficits in synaptic plasticity. These adaptations may contribute to the cognitive deficits associated with chronic toluene exposure and provide novel molecular targets for preventing long-term neurophysiological abnormalities following chronic toluene inhalation.

MPFC spindle cycles organize sparse thalamic activation and recently active CA1 cells during non-REM sleep.

Sleep oscillations in the neocortex and hippocampus are critical for the integration of new memories into stable generalized representations in neocortex. However, the role of the thalamus in this process is poorly understood. To determine the thalamic contribution to non-REM oscillations (sharp-wave ripples, SWRs; slow/delta; spindles), we recorded units and local field potentials (LFPs) simultaneously in the limbic thalamus, mPFC, and CA1 in rats. We report that the cycles of neocortical spindles provide a key temporal window that coordinates CA1 SWRs with sparse but consistent activation of thalamic units. Thalamic units were phase-locked to delta and spindles in mPFC, and fired at consistent lags with other thalamic units within spindles, while CA1 units that were active during spatial exploration were engaged in SWR-coupled spindles after behavior. The sparse thalamic firing could promote an incremental integration of recently acquired memory traces into neocortical schemas through the interleaved activation of thalamocortical cells.

Pubertal stress decreases sexual motivation and supresses the relation between cerebral theta rhythms and testosterone levels in adult male rats

This study evaluated the effect of stress during puberty on sexual motivation and the correlation between serum testosterone levels (T) and the absolute power of the theta electroencephalographic rhythms, recorded in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) of adult male rats. Thirty males of the stressed group (SG, housed 1 per cage from days 25–50) and 30 controls (CG, housed 5 per cage), were tested in copulatory interactions at 90 days of age. The above mentioned physiological parameters were obtained during the awake-quiet state in a sub-group without sexual motivation (WSM, n = 15, stimulated with a nonreceptive female) and a sub-group with sexual motivation (SM, n = 15, stimulated with a receptive-female). Pearson correlations (r) between these parameters were calculated for each sub-group and brain structure and then compared between sub-groups. SG presented higher mount and intromission latencies than CG. While CG-WSM showed a positive r between T levels and theta band (0.23-0.59), those CG-SM presented a negative r (−0.23 to −0.67). An r that tended towards zero (−0.31 to 0.29) was obtained in both stressed sub-groups. This study shows that pubertal stress suppresses the relation between serum T levels and theta rhythms in the mPFC and BLA in adult male rats. This is one of the first studies evaluating the association between these two physiological parameters specifically in the context of sexual motivation; thus increasing our understanding of the effect of pubertal stress on prefrontal-amygdaline functioning during the sexually-motivated state in male rats.

Repeated Fluoxetine Treatment Induces Transient Morphological Changes in the Medial Prefrontal Cortex of Adult Male Rats

Fluoxetine (Flx) is widely used to treat mood and anxiety disorders. Many studies report the Flx-induced neurotrophic effects and morphological changes in the medial prefrontal cortex (mPFC) of adult rats. However, whether these changes are lasting and how astrocytes take part in are still not clear. This study aims to detect how Flx effect the astrocytes and morphological changes and whether these changes are lasting.