Search

Elucidating the neural mechanisms of memory in the brain is a central goal of neuroscience. Here, we discuss modern‐day transcriptomics methodologies, and how they are well‐poised to revolutionize our insight into memory mechanisms at unprecedented resolution and throughput. Focusing on the hippocampus and amygdala, two regions extensively examined in memory research, we show how single‐cell transcriptomics technologies have been leveraged to understand the naïve state of these brain regions. Building upon this foundation, we show that these technologies can be applied to single‐trial learning paradigms to comprehensively identify molecules and cells that participate in the encoding and retrieval of memory. Transcriptomics also provides an opportunity to understand the cell‐type organization of the human hippocampus and amygdala, and due to conservation of these brain regions between humans and rodents, to infer behavioral and causal contributions in the human brain by leveraging rodent cell‐type homologies and interventions. Ultimately, such transcriptomic technologies are poised to usher in a qualitatively novel understanding of memory in the brain. [ABSTRACT FROM AUTHOR]

This study determined the effects of intranasal pregnenolone (IN‐PREG) on acetylcholine (ACh) levels in selected areas of the rat brain, using in vivo microdialysis. Previous studies showed that PREG rapidly reaches the rodent brain after intranasal administration and that direct infusion of PREG and PREG‐S into the basal forebrain modulates ACh release in frontal cortex, amygdala, and hippocampus. In the present study, we investigated the effects of IN‐PREG on the cholinergic system in the rat brain. In the first experiment, IN‐PREG (5.6 and 11.2 mg/ml) or vehicle was applied bilaterally, and we hypothesized that IN‐PREG would increase ACh levels in amygdala, hippocampus, and frontal cortex, relative to baseline and vehicle. Dialysate was collected for 100 min, based on pilot data of duration of effect. Bilateral IN‐PREG (5.6 and 11.2 mg/ml) increased frontal cortex and hippocampal ACh relative to both baseline and vehicle. Moreover, 11.2 mg/ml PREG increased ACh in the amygdala relative to baseline, the lower dose, and vehicle. Therefore, in the second experiment, IN‐PREG (11.2 mg/ml) was applied only into one nostril, with vehicle applied into the other nostril, in order to determine whether ACh is predominantly increased in the ipsilateral relative to the contralateral amygdala. Unilateral application of IN‐PREG increased ACh in the ipsilateral amygdala, whereas no effect was observed on the contralateral side, suggesting that PREG was transported from the nostrils to the brain via the olfactory epithelial pathway, but not by circulation. The present data provide additional information on IN‐PREG action in the cholinergic system of frontal cortex, amygdala, and hippocampus. This may be relevant for therapeutic IN application of PREG in neurogenerative and neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Angelman syndrome ( AS) is a neuropsychiatric disorder characterized by autism, intellectual disability and motor disturbances. The disease is primarily caused by the loss of function of maternally inherited UBE3A. Ube3a maternal-deficient mice recapitulates many essential feature of AS. These AS mice have been shown to be under chronic stress and exhibits anxiety-like behaviour because of defective glucocorticoid receptor signalling. Here, we demonstrate that chronic stress in these mice could lead to down-regulation of parvalbumin-positive interneurons in the hippocampus and basolateral amygdala from early post-natal days. Down-regulation of parvalbumin-positive interneurons number could be because of decrease in the expression of parvalbumin in these neurons. We also find that treatment with fluoxetine, a selective serotonin reuptake inhibitor, results in restoration of impaired glucocorticoid signalling, elevated serum corticosterone level, parvalbumin-positive interneurons and anxiety-like behaviours. Our findings suggest that impaired glucocorticod signalling in hippocampus and amygdala of AS mice is critical for the decrease in parvalbumin interneurons number, emergence of anxiety and other behavioural deficits and highlights the importance of fluoxetine in the recovery of these abnormalities. [ABSTRACT FROM AUTHOR]

Protein kinase B (also known as Akt) signaling regulates dopamine-mediated locomotor behaviors. Here the ability of cocaine to regulate Akt and glycogen synthase kinase 3 (GSK3) was studied. Rats were injected with cocaine or saline in a binge-pattern, which consisted of three daily injections of 15 mg/kg cocaine or 1 mL/kg saline spaced 1 h apart for 1, 3, or 14 days. Amygdala, nucleus accumbens, caudate putamen, and hippocampus tissues were dissected 30 min following the last injection and analyzed for phosphorylated and total Akt and GSK3(α and β) protein levels using western blot analysis. Phosphorylation of Akt on the threonine-308 (Thr308) residue was significantly reduced in the nucleus accumbens and increased in the amygdala after 1 day of cocaine treatment; however, these effects were not accompanied by a significant decrease in GSK3 phosphorylation. Phosphorylation of Akt and GSK3 was significantly reduced after 14 days of cocaine administration, an effect that was only observed in the amygdala. Cocaine did not alter Akt or GSK3 phosphorylation in the caudate putamen or hippocampus. The findings in nucleus accumbens may reflect dopaminergic motor-stimulant activity caused by acute cocaine, whereas the effects in amygdala may be associated with changes in emotional state that occur after acute and chronic cocaine exposure. [ABSTRACT FROM AUTHOR]

Previous studies indicate that the endocannabinoid system is a potential target for the treatment of depression. To further examine this question we assessed the effects of electroconvulsive shock (ECS) treatment, both a single session and 10 daily sessions, on endocannabinoid content, CB1 receptor binding parameters and CB1 receptor-mediated [35S]GTPγS binding in the prefrontal cortex, hippocampus, hypothalamus and amygdala. A single ECS session resulted in a general reduction in the binding affinity of the CB1 receptor in all brain regions examined, as well as reductions in N-arachidonylethanolamine (anandamide) content in the prefrontal cortex and the hippocampus, reduced hydrolysis of anandamide by fatty acid amide hydrolase (FAAH) in the prefrontal cortex and an increase in the binding site density of the CB1 receptor in the amygdala. Following 10 ECS sessions, all these effects subsided except for the reductions in anandamide content in the prefrontal cortex, which increased in magnitude, as well as the reductions in FAAH activity in the prefrontal cortex. Additionally, repeated ECS treatment resulted in a significant reduction in the binding site density of the CB1 receptor in the prefrontal cortex, but did not alter CB1 receptor-mediated [35S]GTPγS binding. Repeated ECS treatment also significantly enhanced the sensitivity of CB1 receptor-mediated [35S]GTPγS binding in the amygdala. Collectively, these data demonstrate that ECS treatment results in a down-regulation of cortical and an up-regulation of subcortical endocannabinoid activity, illustrating the possibility that the role of the endocannabinoid system in affective illness may be both complex and regionally specific. [ABSTRACT FROM AUTHOR]

The presence of serotonin 1A receptor (5-HT1A-R) in the hippocampus, amygdala, and most regions of the frontal cortex is essential between postnatal day-5–21 (P5–21) for the expression of normal anxiety levels in adult mice. Thus, the 5-HT1A-R plays a crucial role in this time window of brain development. We show that the 5-HT1A-R-mediated stimulation of extracellular signal-regulated kinases 1 and 2 (Erk1/2) in the hippocampus undergoes a transition between P6 and P15. At P6, a protein kinase C (PKC) isozyme is required for the 5-HT1A-R ⇒Erk1/2 cascade, which causes increased cell division in the dentate gyrus. By contrast, at P15, PKCα participates downstream of Erk1/2 to augment synaptic transmission through the Schaffer Collateral pathway but does not cause increased cell division. Our data demonstrate that the 5-HT1A-R ⇒Erk1/2 cascade uses PKC isozymes differentially, first boosting the cell division to form new hippocampal neurons at P6 and then undergoing a plastic change in mechanism to strengthen synaptic connections in the hippocampus at P15. [ABSTRACT FROM AUTHOR]

We examined energy metabolism and amino acid content in the hippocampus of amygdaloid-kindled rats using1H NMR spectroscopy. Three weeks after the last stage 5 seizure, kindled rats were killed by microwave irradiation. The hippocampus was dissected out and subjected to MeOH/CHCl3 extraction. All1H spectra were analyzed to quantify absolute concentrations using a non-linear least squares method, combined with a prior knowledge of chemical shifts. Saturation effects were compensated for by the T1 measurement of each component. Levels of energy metabolism-related compounds, phosphocreatine, creatine, glucose and succinate were the same in both kindled rats and sham controls. Lactate concentration had a tendency to increase, although this was not statistically significant. When compared with sham controls, levels of aspartate, glutamate, glycine and glutamine, as well as GABA and inositol, were increased in the ipsilateral but not the contralateral hippocampus. In contrast, levels of taurine, alanine and threonine were unchanged. Finally,N-acetylaspartylglutamate content was elevated, whereasN-acetyl-l-aspartate content was unaltered in the ipsilateral hippocampus of kindled animals. Our results suggest that amygdala kindling may affects amino acid metabolism, but not energy metabolism. [ABSTRACT FROM AUTHOR]

Prohormone convertase (PC1) is found in endocrine cell lines that express cholecystokinin (CCK) mRNA and process pro CCK to biologically active products. Other studies have demonstrated that PC1 may be a one of the enzymes responsible for the endoproteolytic cleavages that occur in pro CCK during its biosynthesis and processing. Prohormone convertase 1 (PC1) has a distribution that is similar to cholecystokinin (CCK) in rat brain. A moderate to high percentage of CCK mRNA-positive neurons express PC1 mRNA. CCK levels were measured in PC1 knockout and control mice to assess the degree to which loss of PC1 changed CCK content. CCK levels were decreased 62% in hippocampus, 53% in amygdala and 57% in pons-medulla in PC1 knockout mice as compared to controls. These results are highly correlated with the colocalization of CCK and PC1. The majority of CCK mRNA-positive neurons in the pyramidal cell layer of the hippocampus express PC1 mRNA and greater than 50% of CCK mRNA-positive neurons in several nuclei of the amygdala also express PC1. These results demonstrate that PC1 is important for CCK processing. PC2 and PC5 are also widely colocalized with CCK. It may be that PC2, PC5 or another non-PC enzyme are able to substitute for PC1 and sustain production of some amidated CCK. Together these enzymes may represent a redundant system to insure the production of CCK. [ABSTRACT FROM AUTHOR]

Presents several abstracts of studies on learning and memory. "ATPA, A Kainate GluR5 Agonist, Abolishes the Kindling-Induced Impairment of LTP in the Rat Lateral Amygdala," by D. Albrecht and M. Schubert; "Muscarinic Participation in cAMP Signaling in Hippocampus and Striatum," by G. Sánchez, C. Blanco, N. Colettis, D. Jerusalinsky and E. Kornisiuk; "Roles for PLC Gamma 1 and PI-3 Kinase in Long-term Hippocampus Dependent Memory," by S. Blum, A. N. Moore, S. A. Orsi and P. K. Dash.