excitation/inhibition hippocampus

Drugs that target monoaminergic transmission represent a first-line treatment for major depression. Though a full understanding of the mechanisms that underlie antidepressant efficacy is lacking, evidence supports a role for enhanced excitatory transmission. This can occur through two non-mutually exclusive mechanisms. The first involves increased function of excitatory neurons through relatively direct mechanisms such as enhanced dendritic arborization. Another mechanism involves reduced inhibitory function, which occurs with the rapid antidepressant ketamine...

Somatostatin reduces neuronal excitability via somatostatin receptors (Sst1 -Sst5 ) and inhibits seizure activity. However, the expression status of the Sst subtypes in epileptic mice and their role in the antiepileptic effects of somatostatin remain unclear. Here, we show that the Sst subtypes are regulated differently by epileptic neuronal activity in mice. Systemic kainate injection rapidly and transiently elevated the Sst2 and Sst3 mRNA and reduced Sst1 and Sst4 mRNA in the hippocampus; however, among all the subtypes, only Sst2 mRNA was increased in the excitatory neurons of the basolateral amygdala, accompanied by a decrease in the level of Sst2 protein...

Oscillations in the brain facilitate neural processing and cognitive functions. This study investigated the dependence of long-term potentiation (LTP), a neural correlate of memory, on the phase of the hippocampal θ rhythm, a prominent brain oscillation. Multichannel field potentials and current source-sinks were analyzed in hippocampal CA1 of adult male rats under urethane anesthesia. A single burst (five pulses at 200 Hz) stimulation of stratum oriens (OR) induced LTP of the basal dendritic excitatory sink (ES), which was maximal when the burst was delivered at ∼340° and ∼160° of the distal dendritic θ rhythm...

BACKGROUND: Transcranial ultrasonic stimulation is a novel noninvasive tool for neuromodulation, and has high spatial resolution and deep penetration. Although it can increase excitation of neurons, its effects on neuron are poorly understood. This study was to evaluate effect of ultrasonic stimulation (US) on neurons in vitro. In this paper, the effect of US on the excitability and voltage-dependent [Formula: see text] currents of CA1 pyramidal neurons in the rat hippocampus was studied using patch clamp...

Breast cancer patients using aromatase inhibitors (AIs) as an adjuvant therapy often report side effects including hot flashes, mood changes, and cognitive impairment. Despite long-term use in humans, little is known about the effects of continuous AI administration on the brain and cognition. We used a primate model of human cognitive aging, the common marmoset, to examine the effects of a 4-week daily administration of the AI Letrozole (20 μg, p.o.) on cognition, anxiety, thermoregulation, brain estrogen content, and hippocampal pyramidal cell physiology...

KEY POINTS: KCC2 plays a critical role in regulating chloride homeostasis, which is essential for hyperpolarizing inhibition in the mature nervous system. KCC2 interacts with many proteins involved in excitatory neurotransmission, including the GluK2 subunit of the kainate receptor (KAR). We show that activation of KARs hyperpolarizes the reversal potential for GABA (EGABA ) through both ionotropic and metabotropic signalling mechanisms. KCC2 is required for the metabotropic KAR-mediated regulation of EGABA, but ionotropic KAR signalling can hyperpolarize EGABA independent of KCC2 transporter function...

Astrocytes from the hippocampus of chronic epileptic rats exhibit an abnormal pattern of intracellular calcium oscillations, characterized by an augmented frequency of long lasting spontaneous Ca2+ transients, which are sensitive to purinergic receptor antagonists but resistant to tetrodotoxin. The above suggests that alterations in astroglial Ca2+ -dependent excitability observed in the epileptic tissue could arise from changes in astrocyte-to-astrocyte signaling, which is mainly mediated by purines in physiological and pathological conditions...

The purpose of this study was to explore the differences in interhemispheric functional connectivity in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) based on a triple network model consisting of the default mode network (DMN), salience network (SN), and executive control network (ECN). The technique of voxel-mirrored homotopic connectivity (VMHC) analysis was applied to explore the aberrant connectivity of all patients. The results showed that: (1) the statistically significant connections of interhemispheric brain regions included DMN-related brain regions (i...

Adolescence is marked by increased vulnerability to mental disorders and maladaptive behaviors, including anorexia nervosa. Food-restriction (FR) stress evokes foraging, which translates to increased wheel running exercise (EX) for caged rodents, a maladaptive behavior, since it does not improve food access and exacerbates weight loss. While almost all adolescent rodents increase EX following FR, some then become resilient by suppressing EX by the second-fourth FR day, which minimizes weight loss. We asked whether GABAergic plasticity in the hippocampus may underlie this gain in resilience...

Cognitive impairment (CI), a debilitating and pervasive feature of multiple sclerosis (MS), is correlated with hippocampal atrophy. Findings from postmortem MS hippocampi indicate that expression of genes involved in both excitatory and inhibitory neurotransmission are altered in MS, and although deficits in excitatory neurotransmission have been reported in the MS model experimental autoimmune encephalomyelitis (EAE), the functional consequence of altered inhibitory neurotransmission remains poorly understood...

The hippocampus receives extensive cholinergic modulation from the basal forebrain, which has been shown to have a prominent role in attention, learning, and synaptic plasticity. Disruptions of this modulation have been linked to a variety of neural disorders including Alzheimer's Disease. Pyramidal cells of the CA1 region of the hippocampus express several cholinergic receptor types in different locations throughout the cells' morphology. Developing a computational model of these cells and their modulation provides a unique opportunity to explore how each receptor type alters the overall computational role of the cell...

Sharp wave-ripples (140-220 Hz) are patterns of brain activity observed in the local field potential of the hippocampus which are present during memory consolidation. As rodents switch from memory consolidation to memory encoding behaviors, cholinergic inputs to the hippocampus from neurons in the medial septum-diagonal band of Broca cause a marked reduction in ripple incidence. The mechanism for this disruption in ripple power is not fully understood. In isolated neurons, the major effect of cholinergic input on hippocampal neurons is depolarization of the membrane potential, which affects both hippocampal pyramidal neurons and inhibitory interneurons...

Two-pore domain K+ (K2P) channels have been shown to modulate neuronal excitability. The physiological role of TWIK-1, the first identified K2P channel, in neuronal cells is largely unknown, and we reported previously that TWIK-1 contributes to the intrinsic excitability of dentate gyrus granule cells (DGGCs) in mice. In the present study, we investigated the coexpression of TWIK-1 and TASK-3, another K2P member, in DGGCs. Immunohistochemical staining data showed that TASK-3 proteins were highly localized in the proximal dendrites and soma of DGGCs, and this localization is similar to the expression pattern of TWIK-1...

We established the mouse model of fluoride (68 mg F ion/L deionized water) exposure for 90 days, 120 days and 150 days, and applied diverse methods as behavioral models of anxiety and depression, and analyzed the levels of the anxiety- and depression-like related genes like BDNF1, BDNF4, 5-HT1A, VGLUT, GAD67, and VGAT in the mouse hippocampus. In the mice exposed to NaF for 120 days, compared to the control group, chalky opacity was observed on the enamel of teeth; the results of anxiety-like behavior, like elevated zero maze, light/dark exploration test, novel object recognition test and emergence test were significantly altered, however in the mice exposed for 150 days, only the elevated zero maze and emergence test were significantly altered...

Even though pharmacological approaches able to counteract age-dependent cognitive impairment have been highly investigated, drugs improving cognition and memory are still an unmet need. It has been hypothesized that sustaining energy dynamics within the aged hippocampus can boost memory storage by sustaining synaptic functioning and long term potentiation (LTP). Dexpramipexole (DEX) is the first-in-class compound able to sustain neuronal bioenergetics by interacting with mitochondrial F1Fo-ATP synthase. In the present study, for the first time we evaluated the effects of DEX on synaptic fatigue, LTP induction, learning and memory retention...

Group I metabotropic glutamate receptors, in particular mGluR5, have been implicated in various forms of synaptic plasticity that are believed to underlie declarative memory. We observed that mGluR5 specifically activated a channel containing TRPC1, an isoform of the canonical family of transient receptor potential (TRPC) channels highly expressed in CA1-3 regions of the hippocampus. TRPC1 is able to form tetrameric complexes with TRPC4 and/or TRPC5 isoforms. TRPC1/4/5 complexes have recently been involved in the efficiency of synaptic transmission in the hippocampus...

There is strong evidence that immune activation from prenatal infection increases the risk for offspring to develop schizophrenia. The endocannabinoid (eCB) system has been implicated in the pathophysiology of schizophrenia while models of cortical dysfunction postulate an imbalance between neuronal excitation and inhibition in the disorder. The current study examined the impact of prenatal immune activation on eCB-mediated inhibitory mechanisms. We compared two forms of eCB-related plasticity of evoked inhibitory postsynaptic currents, namely depolarization-induced suppression of inhibition (DSI) and metabotropic glutamate receptor-induced long term depression (mGluR-iLTD), in both the dorsal and ventral hippocampus between adolescent offspring from rat dams that received either saline or bacterial lipopolysaccharide (LPS) during pregnancy...

The imbalance between the GABA-mediated inhibition and the glutamate-mediated excitation is the primary pathological mechanism of epilepsy. GABAergic and glutamatergic neurotransmission have become the most important targets for controlling epilepsy. Ginsenoside compound K (GCK) is a main metabolic production of the ginsenoside Rb1, Rb2, and Rc in the intestinal microbiota. Previous studies show that GCK promoted the release of GABA from the hippocampal neurons and enhanced the activity of GABAA receptors. GCK is shown to reduce the expression of NMDAR and to attenuate the function of the NMDA receptors in the brain...

Prepulse modulation (PPM) is an electrophysiological method which enables to assess sensory processing in vivo. Reflex responses may be facilitated or inhibited (prepulse inhibition, PPI) after a weak stimulus. Theoretically, in animal studies, the generator of PPI involves pedunculopontine nucleus which is modulated by various structures, including amygdala. We aimed to investigate whether or not there was a role of limbic structures in the generation of PPM in humans. For this purpose, we studied PPM of the blink reflex (BR) in 10 patients with mesial temporal lobe epilepsy (MTLE group) and in nine patients who had previously undergone amygdala resection for medically resistant MTLE (surgery group)...

The CA3 subregion of the hippocampus is important for rapid encoding, storage and retrieval of associative memories. Lesions and pharmacological inhibitions of hippocampal CA3 suggest that it is essential for different memories. However, how CA3 functions in spatial and episodic memory in different time scales (i.e. short-term versus long term) without permanent lesions has not been systematically investigated yet. Taking advantage of the chemogenetic access to opsins, this study used luminopsins, fusion proteins of luciferase and optogenetic elements, to manipulate neuronal activity in CA3 during memory tasks over a range of spatial and temporal scales...