Limbic Areas Research Articles

Ventral tegmental area GABA neurons mediate stress-induced blunted reward-seeking in mice

Decreased pleasure-seeking (anhedonia) forms a core symptom of depression. Stressful experiences precipitate depression and disrupt reward-seeking, but it remains unclear how stress causes anhedonia. We recorded simultaneous neural activity across limbic brain areas as mice underwent stress and discovered a stress-induced 4 Hz oscillation in the nucleus accumbens (NAc) that predicts the degree of subsequent blunted reward-seeking. Surprisingly, while previous studies on blunted reward-seeking focused on dopamine (DA) transmission from the ventral tegmental area (VTA) to the NAc, we found that VTA GABA, but not DA, neurons mediate stress-induced blunted reward-seeking. Inhibiting VTA GABA neurons disrupts stress-induced NAc oscillations and rescues reward-seeking. By contrast, mimicking this signature of stress by stimulating NAc-projecting VTA GABA neurons at 4 Hz reproduces both oscillations and blunted reward-seeking. Finally, we find that stress disrupts VTA GABA, but not DA, neural encoding of reward anticipation. Thus, stress elicits VTA-NAc GABAergic activity that induces VTA GABA mediated blunted reward-seeking.

Resting-State Network Alterations Differ between Alzheimer's Disease Atrophy Subtypes.

Several Alzheimer's disease (AD) atrophy subtypes were identified, but their brain network properties are unclear. We analyzed data from two independent datasets, including 166 participants (103AD/63 controls) from the DZNE-longitudinal cognitive impairment and dementia study and 151 participants (121AD/30 controls) from the AD neuroimaging initiative cohorts, aiming to identify differences between AD atrophy subtypes in resting-state functional magnetic resonance imaging intra-network connectivity (INC) and global and nodal network properties. Using a data-driven clustering approach, we identified four AD atrophy subtypes with differences in functional connectivity, accompanied by clinical and biomarker alterations, including a medio-temporal-predominant (S-MT), a limbic-predominant (S-L), a diffuse (S-D), and a mild-atrophy (S-MA) subtype. S-MT and S-D showed INC reduction in the default mode, dorsal attention, visual and limbic network, and a pronounced reduction of "global efficiency" and decrease of the "clustering coefficient" in parietal and temporal lobes. Despite severe atrophy in limbic areas, the S-L exhibited only marginal global network but substantial nodal network failure. S-MA, in contrast, showed limited impairment in clinical and cognitive scores but pronounced global network failure. Our results contribute toward a better understanding of heterogeneity in AD with the detection of distinct differences in functional connectivity networks accompanied by CSF biomarker and cognitive differences in AD subtypes.

The influence of conditioned stimuli on [11C]-(+)-PHNO PET binding in tobacco smokers after a one week abstinence

Stimuli previously paired with drugs of dependence can produce cravings that are associated with increased dopamine (DA) levels in limbic and striatal brain areas. Positron Emission Tomography (PET) imaging with [11C]-(+)-PHNO allows for a sensitive measurement of changes in DA levels. The purpose of the present study was to investigate changes in DA levels, measured with PET imaging with [11C]-(+)-PHNO, in regions of interest in smokers who had maintained abstinence for 7–10 days. Participants (N = 10) underwent two PET scans on separate days, during which they viewed either smoking-related or neutral images, in counterbalanced order. Craving was measured with the 12-item Tobacco Craving Questionnaire (TCQ) and the Questionnaire on Smoking Urges-Brief (QSU-B). Compared to neutral cues, smoking cues did not increase craving. There were no changes in [11C]-(+)-PHNO binding in the cue condition compared to the neutral condition for most regions of interest (ventral pallidum, globus pallidus, limbic striatum, associative striatum, sensorimotor striatum). However, binding potential in the substantia nigra was greater in the smoking-cue condition, indicating decreased synaptic dopamine. There is a potential change of DA level occurring in midbrain following the presentation of smoking-related cues. However, this preliminary finding would need to be validated with a larger sample.

CMF and MET treatment induce cognitive impairment through upregulation of IL-1α in rat brain.

Cyclophosphamide (CYP), methotrexate (MTX) and 5-fluorouracil (5-FU) (CMF) are chemotherapeutic agents known to cause acute and long-term cognitive impairment in cancer patients. Cognitive function is regulated mainly by neuronal circuitry in the brain, especially the cortex and hippocampus as well as other components of the limbic area. Neuroinflammation mediated by proinflammatory cytokines is a well-known cause of cognitive impairment. Our previous study showed that metformin induced cognitive impairment and neuroinflammation in CMF-treated rats. Understanding the effects and mechanisms of CMF and MET treatment on chemotherapy-related cognitive impairment and the relationship with neuroinflammation may help prevent some of the adverse effects of this type of chemotherapy in cancer patients. Rats were divided into four groups: control (normal saline), CMF (50 mg/kg CYP, 2 mg/kg MTX, 50 mg/kg 5-FU; two doses administered by intraperitoneal injection over two weeks), MET (2.5 mg/ml - oral administration daily), and CMF+MET group. IL-1α, IRS-1, Akt-a and TNF-α levels in brain tissues were measured by ELISA and data were analyzed by one-way ANOVA test followed by Tukey's test. Compared with the control group, IL-1α levels were significantly increased in the CMF+MET group, whereas there were no significant differences in the MET and CMF groups. On the other hand, IRS-1, TNF-α and Akt-a expression and mitochondrial complex 1 activity indicated that systemic CMF and MET treatment did not change the expression of these proteins in the brain compared to the control group. Our results indicate that cognitive function is impaired by the administration of two doses of CMF and MET over a period of two weeks as a result of IL-1α overexpression in the brain.

Corpus Callosum and Its Connections: A Fiber Dissection Study

We performed a fine white fiber dissection to demonstrate the extensive connections of the corpus callosum. Three formalin-fixed frozen cadaveric human brain specimens were dissected using Klingler's technique. On one half of each hemisphere, the superior connections of the corpus callosum were dissected and in the other half the inferior connections of the corpus callosum were dissected. The mean length of the corpus callosum from the rostrum to the splenium was 7.8 cm. The fibers of the corpus callosum were classified as superior/dorsal radiations, inferior/ventral radiations, anterior radiations, and posterior radiations. The entire transverse length of the dorsal callosal radiation from one hemisphere to the other was 8.1 cm. For anterior interhemispheric approaches, an incision in the anterior part of the body not extending beyond 3.5 cm from the genu was found to be safe with regards to crossing motor fibers. The corpus callosum was found to have intricate connections with all the lobes of the cerebral hemispheres, including the insular region and the limbic and paralimbic areas. Based on the course and traverse of the callosal fibers, a transverse incision in the corpus callosum should be preferred when performing a callosotomy to access intraventricular lesions as this splits the callosal fibers instead of transecting them. The analysis of the course of the callosal radiations enhances understanding of the growth pattern of primary corpus callosal gliomas and helps to design a safe surgical strategy.

Prior exposure to Hedione, a model of pheromone, does not affect female ratings of male facial attractiveness or likeability

The existence of pheromones in humans is controversial, partly because of definitional difficulties and partly because of the question of possible chemical substances. The synthetic compound Methyl dihydrojasmonate (Hedione) is potent to bind to vomeronasal-type 1 receptors (VN1R1s) and activate limbic areas of the brain in a sex-specific manner. However, one of the most important definitional points for a human pheromone effect has not yet been investigated, i.e., whether smelling Hedione, a model of pheromone, has a behavioral effect. We tested in females whether Hedione leads to altered perception of male social stimuli. Each of the included women were sensitive to Hedione and were tested around the time of ovulation in three consecutive sessions, during each they were exposed to either Hedione or Phenylethyl alcohol or Odorless air. We measured the speed of male face recognition (implicit priming task) and collected ratings of facial attractiveness and likeability of men (explicit task). Only about half of the women tested were sensitive to Hedione. Those women did not show any effect of Hedione exposure in the implicit priming task and moderate, but non-significant effects in the explicit task. We therefore assume that Hedione is not a potent model of pheromone in humans and this observation may be due to the fact that the artificially produced substance is not suited for signaling the proximity of other humans. Furthermore, the high rate of Hedione-specific anosmia leads to the hypothesis that a substantial proportion of individuals has a poor V1NR1 receptor expression.

The costs of over-control in anorexia nervosa: evidence from fMRI and ecological momentary assessment

A growing body of evidence suggests that a high level of self-control may, despite its positive effects, influence cognitive processing in an unfavorable manner. However, the affective costs of self-control have only rarely been investigated. Anorexia nervosa (AN) is an eating disorder that is often characterized by excessive self-control. Here, we used fMRI to explore whether over-control in AN may have negative affective consequences. 36 predominantly adolescent female AN patients and 36 age-matched healthy controls (HC) viewed negative and neutral pictures during two separate fMRI sessions before and after 10 min of rest. We tested whether abnormally elevated neural activity during the initial presentation in a brain region broadly implicated in top-down control, the dorsolateral prefrontal cortex (dlPFC), could predict subsequent activation in limbic areas relevant to bottom-up affective processing. Using ecological momentary assessment (EMA), we also tested for associations between the aforementioned neuroimaging markers and negative affective states in the two weeks following the experiment. fMRI data revealed that higher initial activation of the dlPFC in AN predicted increased amygdala reactivity during the second fMRI session, which in turn was related to increased self-reported tension during two weeks following the scan. These data suggest that over-control in AN patients may come at a cost including negative affective states on a short (minutes) as well as a longer time scale (days). This mechanism may significantly contribute to the persistence of AN.

Early-life stress induces genome-wide sex-dependent miRNA expression and correlation across limbic brain areas in rats.

Aims:The aim of this study was to assess regional- and sex-dependent changes in miRNA expression resulting from early-life stress (ELS).Materials and methods:Small RNA sequencing was used to determine sex-dependent changes in miRNAs after maternal separation, a rodent model of ELS, across the prefrontal cortex, amygdala and hippocampus.Results:Maternal separation induced anhedonia and altered miRNA expression in a sex-dependent manner, particularly in the prefrontal cortex and hippocampus. Gene ontology revealed that these miRNAs target genes with brain-specific biological functions.Conclusion:Using a network approach to explore miRNA signaling across the brain after ELS, regional differences were highlighted as key to studying the brain’s stress response, which indicates that sex is critical for understanding miRNA-mediated ELS-induced behavior.

Analgesic and Antidepressant Effects of the Clinical Glutamate Modulators Acetyl-L-Carnitine and Ketamine.

Pain and depression are leading causes of disability and of profound social and economic burden. Their impact is aggravated by their chronicity and comorbidity and the insufficient efficacy of current treatments. Morphological and functional metabolism studies link chronic pain and depressive disorders to dysfunctional neuroplastic changes in fronto-limbic brain regions that control emotional responses to painful injuries and stressful events. Glutamate modulators are emerging new therapies targeting dysfunctional brain areas implicated in the generation and maintenance of chronic pain and depression. Here, we report the effects of two clinically approved glutamate modulators: acetyl-L-carnitine (ALCAR) and S, R(±)ketamine (KET). ALCAR is a natural neurotrophic compound currently marketed for the treatment of neuropathies. KET is the prototypical non-competitive antagonist at N-methyl-D-aspartate glutamate receptors and a clinically approved anesthetic. Although they differ in pharmacological profiles, ALCAR and KET both modulate aminergic and glutamatergic neurotransmissions and pain and mood. We assessed in rats the effects of ALCAR and KET on cerebral metabolic rates for glucose (rCMRglc) and assessed clinically the effects of ALCAR in chronic pain and of KET in post-operative pain. ALCAR and KET increased rCMRglc at similar degrees in prefrontal, somatosensory, and cingulate cortices, and KET increased rCMRglc at a different, much larger, degree in limbic and dopaminergic areas. While rCMRglc increases in prefrontal cortical areas have been associated with analgesic and antidepressant effects of ALCAR and KET, the marked metabolic increases KET induces in limbic and dopaminergic areas have been related to its psychotomimetic and abuse properties. In patients with chronic neuropathic pain, ALCAR (1,000 mg/day) yielded to a fast (2 weeks) improvement of mood and then of pain and quality of life. In day-surgery patients, KET improved dischargeability and satisfaction. In obese patients undergoing bariatric surgery, a single, low dose of KET (0.5 mg/kg) at induction of anesthesia determined a very fast (hours) amelioration of post-operative depression and pain and an opioid-sparing effect. These findings indicate that ALCAR and KET, two non-selective glutamate modulators, still offer viable therapeutic options in comorbid pain and depression.

Different Alterations of Agonist and Antagonist Binding to 5-HT1A Receptor in a Rat Model of Parkinson's Disease and Levodopa-Induced Dyskinesia: A MicroPET Study.

The gold-standard treatment for Parkinson's disease is L-DOPA, which in the long term often leads to levodopa-induced dyskinesia. Serotonergic neurons are partially responsible for this, by converting L-DOPA into dopamine leading to its uncontrolled release as a "false neurotransmitter". The stimulation of 5-HT1A receptors can reduce involuntary movements but this mechanism is poorly understood. This study aimed to investigate the functionality of 5-HT1A receptors using positron emission tomography in hemiparkinsonian rats with or without dyskinesia induced by 3-weeks daily treatment with L-DOPA. Imaging sessions were performed "off" L-DOPA. Each rat underwent a positron emission tomography scan with [18F]F13640, a 5-HT1AR agonist which labels receptors in a high affinity state for agonists, or with [18F]MPPF, a 5-HT1AR antagonist which labels all the receptors. There were decreases of [18F]MPPF binding in hemiparkinsonian rats in cortical areas. In dyskinetic animals, changes were slighter but also found in other regions. In hemiparkinsonian rats, [18F]F13640 uptake was decreased bilaterally in the globus pallidus and thalamus. On the non-lesioned side, binding was increased in the insula, the hippocampus and the amygdala. In dyskinetic animals, [18F]F13640 binding was strongly increased in cortical and limbic areas, especially in the non-lesioned side. These data suggest that agonist and antagonist 5-HT1A receptor-binding sites are differently modified in Parkinson's disease and levodopa-induced dyskinesia. In particular, these observations suggest a substantial involvement of the functional state of 5-HT1AR in levodopa-induced dyskinesia and emphasize the need to characterize this state using agonist radiotracers in physiological and pathological conditions.

Data-driven parcellation and graph theory analyses to study adolescent mood and anxiety symptoms

Adolescence is a period of rapid brain development when psychiatric symptoms often first emerge. Studying adolescents may therefore facilitate the identification of neural alterations early in the course of psychiatric conditions. Here, we sought to utilize new, high-quality brain parcellations and data-driven graph theory approaches to characterize associations between resting-state networks and the severity of depression, anxiety, and anhedonia symptoms—salient features across psychiatric conditions. As reward circuitry matures considerably during adolescence, we examined both Whole Brain and three task-derived reward networks. Subjects were 87 psychotropic-medication-free adolescents (age = 12–20) with diverse psychiatric conditions (n = 68) and healthy controls (n = 19). All completed diagnostic interviews, dimensional clinical assessments, and 3T resting-state fMRI (10 min/2.3 mm/TR = 1 s). Following high-quality Human Connectome Project-style preprocessing, multimodal surface matching (MSMAll) alignment, and parcellation via the Cole-Anticevic Brain-wide Network Partition, weighted graph theoretical metrics (Strength Centrality = CStr; Eigenvector Centrality = CEig; Local Efficiency = ELoc) were estimated within each network. Associations with symptom severity and clinical status were assessed non-parametrically (two-tailed pFWE < 0.05). Across subjects, depression scores correlated with ventral striatum CStr within the Reward Attainment network, while anticipatory anhedonia correlated with CStr and ELoc in the subgenual anterior cingulate, dorsal anterior cingulate, orbitofrontal cortex, caudate, and ventral striatum across multiple networks. Group differences and associations with anxiety were not detected. Using detailed functional and clinical measures, we found that adolescent depression and anhedonia involve increased influence and communication efficiency in prefrontal and limbic reward areas. Resting-state network properties thus reflect positive valence system anomalies related to discrete reward sub-systems and processing phases early in the course of illness.

Cortical and subcortical hemodynamic changes during sleep slow waves in human light sleep

EEG slow waves, the hallmarks of NREM sleep are thought to be crucial for the regulation of several important processes, including learning, sensory disconnection and the removal of brain metabolic wastes. Animal research indicates that slow waves may involve complex interactions within and between cortical and subcortical structures. Conventional EEG in humans, however, has a low spatial resolution and is unable to accurately describe changes in the activity of subcortical and deep cortical structures. To overcome these limitations, here we took advantage of simultaneous EEG-fMRI recordings to map cortical and subcortical hemodynamic (BOLD) fluctuations time-locked to slow waves of light sleep. Recordings were performed in twenty healthy adults during an afternoon nap. Slow waves were associated with BOLD-signal increases in the posterior brainstem and in portions of thalamus and cerebellum characterized by preferential functional connectivity with limbic and somatomotor areas, respectively. At the cortical level, significant BOLD-signal decreases were instead found in several areas, including insula and somatomotor cortex. Specifically, a slow signal increase preceded slow-wave onset and was followed by a delayed, stronger signal decrease. Similar hemodynamic changes were found to occur at different delays across most cortical brain areas, mirroring the propagation of electrophysiological slow waves, from centro-frontal to inferior temporo-occipital cortices. Finally, we found that the amplitude of electrophysiological slow waves was positively related to the magnitude and inversely related to the delay of cortical and subcortical BOLD-signal changes. These regional patterns of brain activity are consistent with theoretical accounts of the functions of sleep slow waves.

Intracortical Functional Connectivity Predicts Arousal to Noxious Stimuli during Sleep in Humans.

Nociceptive stimuli disrupt sleep, but may, or may not, entail an arousal. While arousal reactions go along with the activation of a widespread cortical network, the factors enabling such activation remain unknown. Here we used intracranial EEG in humans to test the relation between the cortical activity immediately preceding a noxious stimulus and the capacity of such a stimulus to trigger arousal. Intracranial EEG signals were analyzed during all-night sleep in 14 epileptic patients (4 women), who received laser stimuli slightly above their individual pain threshold. During 5 s preceding each stimulus, the functional correlation (spectral phase-coherence) between the main spinothalamic sensory area (posterior insula) and 12 other brain regions, grouped in four networks, as well as their spectral contents, were contrasted according to the presence of a stimulus-induced arousal, and then fed into a logistic regression model to assess their predictive value. Enhanced prestimulus phase-coherence between the sensory posterior insula and neocortical and limbic areas increased significantly the probability of arousal to nociceptive stimuli, in both slow-wave (N2) and rapid eye movements/paradoxical sleep. Furthermore, during N2 sleep, arousal was facilitated by stimulus delivery in periods of attenuated slow-wave activity. Together, these data indicate that sleep micro-states with enhanced interareal communication facilitate information transfer from sensory to higher-order cortical areas, and hence physiological arousal.SIGNIFICANCE STATEMENT Sleep is commonly subdivided into stages based on specific electrophysiological characteristics; however, within each single sleep stage, the functional state of the brain is continuously changing. Here we show that the probability for a phasic noxious stimulus to entail an arousal is modulated by the prestimulus interareal phase-coherence between sensory and higher-level cortical areas. Fluctuations in interareal communication immediately before the noxious stimulus may determine the responsiveness to incoming input by facilitating or preventing the transfer of noxious information from sensory to multiple higher-level cortical networks.

Network-level functional topological changes after mindfulness-based cognitive therapy in mood dysregulated adolescents at familial risk for bipolar disorder: a pilot study

BackgroundGiven that psychopharmacological approaches routinely used to treat mood-related problems may result in adverse outcomes in mood dysregulated adolescents at familial risk for bipolar disorder (BD), Mindfulness-Based Cognitive Therapy for Children (MBCT-C) provides an alternative effective and safe option. However, little is known about the brain mechanisms of beneficial outcomes from this intervention. Herein, we aimed to investigate the network-level neurofunctional effects of MBCT-C in mood dysregulated adolescents.MethodsTen mood dysregulated adolescents at familial risk for BD underwent a 12-week MBCT-C intervention. Resting-state functional magnetic resonance imaging (fMRI) was performed prior to and following MBCT-C. Topological metrics of three intrinsic functional networks (default mode network (DMN), fronto-parietal network (FPN) and cingulo-opercular network (CON)) were investigated respectively using graph theory analysis.ResultsFollowing MBCT-C, mood dysregulated adolescents showed increased global efficiency and decreased characteristic path length within both CON and FPN. Enhanced functional connectivity strength of frontal and limbic areas were identified within the DMN and CON. Moreover, change in characteristic path length within the CON was suggested to be significantly related to change in the Emotion Regulation Checklist score.Conclusions12-week MBCT-C treatment in mood dysregulated adolescents at familial risk for BD yield network-level neurofunctional effects within the FPN and CON, suggesting enhanced functional integration of the dual-network. Decreased characteristic path length of the CON may be associated with the improvement of emotion regulation following mindfulness training. However, current findings derived from small sample size should be interpreted with caution. Future randomized controlled trials including larger samples are critical to validate our findings.

Selective attention to emotional stimuli and emotion recognition in patients with major depression: The role of mineralocorticoid and glutamatergic NMDA receptors.

Mineralocorticoid receptors (MR) are highly expressed in limbic brain areas and prefrontal cortex, which are closely related to selective attention to emotional stimuli and emotion recognition. Patients with major depressive disorder (MDD) show alterations in MR functioning and both cognitive processes. MR stimulation improves cognitive processes in MDD and leads to glutamate release that binds upon N-methyl-D-aspartate receptors (NMDA-R). We examined (1) whether MR stimulation has beneficial effects on selective attention to emotional stimuli and on emotion recognition and (2) whether these advantageous effects can be improved by simultaneous NMDA-R stimulation. We examined 116 MDD patients and 116 healthy controls matched for age (M = 34 years), sex (78% women), and education in the following conditions: no pharmacological stimulation (placebo), MR stimulation (0.4 mg fludrocortisone + placebo), NMDA-R stimulation (placebo + 250 mg D-cycloserine (DCS)), MR + NMDA-R stimulation (fludrocortisone + DCS). An emotional dot probe task and a facial emotion recognition task were used to measure selective attention to emotional stimuli and emotion recognition. Patients with MDD and healthy individuals did not differ in task performance. MR stimulation had no effect on both cognitive processes in both groups. Across groups, NMDA-R stimulation had no effect on selective attention but showed a small effect on emotion recognition by increasing accuracy to recognize angry faces. Relatively young unmedicated MDD patients showed no depression-related cognitive deficits compared with healthy controls. Separate MR and simultaneous MR and NMDA-R stimulation revealed no advantageous effects on cognition, but NMDA-R might be involved in emotion recognition.

Whole-brain mapping of monosynaptic inputs to midbrain cholinergic neurons

The cholinergic midbrain is involved in a wide range of motor and cognitive processes. Cholinergic neurons of the pedunculopontine (PPN) and laterodorsal tegmental nucleus (LDT) send long-ranging axonal projections that target sensorimotor and limbic areas in the thalamus, the dopaminergic midbrain and the striatal complex following a topographical gradient, where they influence a range of functions including attention, reinforcement learning and action-selection. Nevertheless, a comprehensive examination of the afferents to PPN and LDT cholinergic neurons is still lacking, partly due to the neurochemical heterogeneity of this region. Here we characterize the whole-brain input connectome to cholinergic neurons across distinct functional domains (i.e. PPN vs LDT) using conditional transsynaptic retrograde labeling in ChAT::Cre male and female rats. We reveal that input neurons are widely distributed throughout the brain but segregated into specific functional domains. Motor related areas innervate preferentially the PPN, whereas limbic related areas preferentially innervate the LDT. The quantification of input neurons revealed that both PPN and LDT receive similar substantial inputs from the superior colliculus and the output of the basal ganglia (i.e. substantia nigra pars reticulata). Notably, we found that PPN cholinergic neurons receive preferential inputs from basal ganglia structures, whereas LDT cholinergic neurons receive preferential inputs from limbic cortical areas. Our results provide the first characterization of inputs to PPN and LDT cholinergic neurons and highlight critical differences in the connectome among brain cholinergic systems thus supporting their differential roles in behavior.

Single cell plasticity and population coding stability in auditory thalamus upon associative learning

Cortical and limbic brain areas are regarded as centres for learning. However, how thalamic sensory relays participate in plasticity upon associative learning, yet support stable long-term sensory coding remains unknown. Using a miniature microscope imaging approach, we monitor the activity of populations of auditory thalamus (medial geniculate body) neurons in freely moving mice upon fear conditioning. We find that single cells exhibit mixed selectivity and heterogeneous plasticity patterns to auditory and aversive stimuli upon learning, which is conserved in amygdala-projecting medial geniculate body neurons. Activity in auditory thalamus to amygdala-projecting neurons stabilizes single cell plasticity in the total medial geniculate body population and is necessary for fear memory consolidation. In contrast to individual cells, population level encoding of auditory stimuli remained stable across days. Our data identifies auditory thalamus as a site for complex neuronal plasticity in fear learning upstream of the amygdala that is in an ideal position to drive plasticity in cortical and limbic brain areas. These findings suggest that medial geniculate body’s role goes beyond a sole relay function by balancing experience-dependent, diverse single cell plasticity with consistent ensemble level representations of the sensory environment to support stable auditory perception with minimal affective bias.

Neonatal programming with sex hormones: Effect on expression of dopamine D1 receptor and neurotransmitters release in nucleus accumbens in adult male and female rats

Steroid sex hormones produce physiological effects in reproductive and non-reproductive tissues, such as the brain. In the brain, sex hormones receptors are expressed in cortical, limbic and midbrain areas modulating memory, arousal, fear and motivation between other behaviors. One neurotransmitters system regulated by sex hormones is dopamine (DA), where during adulthood, sex hormones promote neurophysiological and behavioral effects on DA systems such as tuberoinfundibular (prolactin secretion), nigrostriatal (motor circuit regulation) and mesocorticolimbic (driving of motivated behavior). However, the long-term effects induced by neonatal exposure to sex hormones on DA release induced by D1 receptor activation and its expression in nucleus accumbens (NAcc) have not been fully studied. To answer this question, neurochemical, cellular and molecular techniques were used. The data show sex differences in NAcc DA extracellular levels induced by D1 receptor activation and protein content of this receptor in male and female control rats. In addition, neonatal programming with a single dose of TP increases the NAcc protein content of D1 receptors of adult male and female rats. Our results show new evidence related with sex differences that could explain the dependence to drug of abuse in males and females, which may be associated with increased reinforcing effects of drugs of abuse.

Endocannabinoid-mediated neuromodulation in the main olfactory bulb at the interface of environmental stimuli and central neural processing.

The olfactory system has become an important functional gateway to understand and analyze neuromodulation since olfactory dysfunction and deficits have emerged as prodromal and, at other times, as first symptoms of many of neurodegenerative, neuropsychiatric and communication disorders. Considering olfactory dysfunction as outcome of altered, damaged and/or inefficient olfactory processing, in the current review, we analyze how olfactory processing interacts with the endocannabinoid signaling system. In the human body, endocannabinoid synthesis is a natural and on-demand response to a wide range of physiological and environmental stimuli. Our current understanding of the response dynamics of the endocannabinoid system is based in large part on research advances in limbic system areas, such as the hippocampus and the amygdala. Functional interactions of this signaling system with olfactory processing and associated pathways are just emerging but appear to grow rapidly with multidimensional approaches. Recent work analyzing the crystal structure of endocannabinoid receptors bound to their agonists in a signaling complex has opened avenues for developing specific therapeutic drugs that could help with neuroinflammation, neurodegeneration, and alleviation/reduction of pain. We discuss the role of endocannabinoids as signaling molecules in the olfactory system and the relevance of the endocannabinoid system for synaptic plasticity.

Pontine hemorrhage as beginning of bipolar disorder or organic mania. A case report

IntroductionPublished evidence describes the appearance of manic episodes in patients who suffer localized brain lesions with no prior psychiatric history.ObjectivesA case report is presented alongside a review of the relevant literature regarding the relationship between Bipolar disorder and strokes.MethodsWe present the case of a 54-year-old man who, after suffering a pontine hemorrhage, developed a depressive mood for which he was treated with Sertraline 50 mg. The following month the patient developed hypomanic mood, disinhibition, insomnia and megalomaniac ideation. He was treated with Risperidone 2 mg and the antidepressant was withdrawn. The symptomology disappeared shortly after but a few months later he developed a major depressive disorder (inhibition, ideas of ruin and guilt, low mood, decreased intake and daily activities…). He was treated again with antidepressants (Citalopram 30mg) and lithium was introduced in the absence of a total response.ResultsMania secondary to brain lesions has been observed in multiple studies, where an association is made mainly with lesions at the frontal, temporal, subcortical limbic brain areas and in lesions causing hypofunctionality on the right side. Most of the cases described occurred in male patients with no prior psychiatric record and with associated vascular risk.ConclusionsIt is important to carry out an exhaustive medical history to be able to identify the cases of secondary mania so as not to ignore the underlying neurological condition in the approach.DisclosureNo significant relationships.