Transmission In Area CA1 Of Hippocampus Research Articles

Increasing astrogenesis in the developing hippocampus induces autistic-like behavior in mice via enhancing inhibitory synaptic transmission.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized primarily by impaired social communication and rigid, repetitive, and stereotyped behaviors. Many studies implicate abnormal synapse development and the resultant abnormalities in synaptic excitatory–inhibitory (E/I) balance may underlie many features of the disease, suggesting aberrant neuronal connections and networks are prone to occur in the developing autistic brain. Astrocytes are crucial for synaptic formation and function, and defects in astrocytic activation and function during a critical developmental period may also contribute to the pathogenesis of ASD. Here, we report that increasing hippocampal astrogenesis during development induces autistic‐like behavior in mice and a concurrent decreased E/I ratio in the hippocampus that results from enhanced GABAergic transmission in CA1 pyramidal neurons. Suppressing the aberrantly elevated GABAergic synaptic transmission in hippocampal CA1 area rescues autistic‐like behavior and restores the E/I balance. Thus, we provide direct evidence for a developmental role of astrocytes in driving the behavioral phenotypes of ASD, and our results support that targeting the altered GABAergic neurotransmission may represent a promising therapeutic strategy for ASD.

Effects of diazepam on glutamatergic synaptic transmission in the hippocampal CA1 area of rats with traumatic brain injury.

The activity of the Schaffer collaterals of hippocampal CA3 neurons and hippocampal CA1 neurons has been shown to increase after fluid percussion injury. Diazepam can inhibit the hyperexcitability of rat hippocampal neurons after injury, but the mechanism by which it affects excitatory synaptic transmission remains poorly understood. Our results showed that diazepam treatment significantly increased the slope of input-output curves in rat neurons after fluid percussion injury. Diazepam significantly decreased the numbers of spikes evoked by super stimuli in the presence of 15 μmol/L bicuculline, indicating the existence of inhibitory pathways in the injured rat hippocampus. Diazepam effectively increased the paired-pulse facilitation ratio in the hippocampal CA1 region following fluid percussion injury, reduced miniature excitatory postsynaptic potentials, decreased action-potential-dependent glutamine release, and reversed spontaneous glutamine release. These data suggest that diazepam could decrease the fluid percussion injury-induced enhancement of excitatory synaptic transmission in the rat hippocampal CA1 area.

SKF83959 suppresses excitatory synaptic transmission in rat hippocampus via a dopamine receptor‐independent mechanism

Dopamine (DA) profoundly modulates excitatory synaptic transmission and synaptic plasticity in the brain. In the present study the effects of SKF83959, the selective agonist of phosphatidylinositol (PI)-linked D(1) -like receptor, on the excitatory synaptic transmission were investigated in rat hippocampus. SKF83959 (10-100 μM) reversibly suppressed the field excitatory postsynaptic potential (fEPSP) elicited by stimulating the Schaffer's collateral-commissural fibers in CA1 area of hippocampal slices. However, the inhibition was not blocked by the D(1) receptor antagonist SCH23390, the D(2) receptor antagonist raclopride, the 5-HT(2A/2C) receptor antagonist mesulergine, or the α(1) -adrenoceptor antagonist prazosin. In addition, SKF83959 inhibited the afferent volley and significantly reduced the paired-pulse facilitation ratios. In dissociated hippocampal CA1 pyramidal neurons, SKF83959 had no detectable effect on glutamate-induced currents but potently inhibited voltage-activated Na(+) current (IC50 value = 26.9 ± 1.0 μM), which was not blocked by SCH23390 or by intracellular dialysis of GDP-β-S. These results demonstrate that SKF83959 suppressed the excitatory synaptic transmission in hippocampal CA1 area, which was independent of D(1) -like receptor. The mechanism underlying the effect could be mainly inhibition of Na(+) channel in the afferent fibers. The suppression of excitatory synaptic transmission and the Na(+) channel by SKF83959 may contribute to its therapeutic benefits in Parkinson's disease.

Effects of Pb 2+ on muscarinic modulation of glutamatergic synaptic transmission in rat hippocampal CA1 area

Lead (Pb 2+) is a pollutant commonly found in the environment. It causes a wide variety of detrimental effects on developing central nervous system. However, the mechanisms of its neurotoxicity remained to be elucidated. In hippocampus, the muscarinic cholinergic system modulates certain forms of synaptic transmission and plasticity, and plays an important role in learning and memory. In this study, the effects of Pb 2+ on muscarinic modulation of glutamatergic synaptic transmission in hippocampal CA1 area were investigated using the conventional whole-cell patch-clamp technique in rat hippocampal slices. In the presence of nicotinic antagonist mecamylamine, carbachol (CCh), a cholinergic agonist, concentration-dependently inhibited glutamatergic excitatory postsynaptic currents (EPSCs), enhanced paired-pulse facilitation (PPF) and the response to 10-Hz pulse-trains. The analysis of the spontaneous excitatory postsynaptic currents (sEPSCs) showed the activation of muscarinic receptors by CCh decreased the frequency, amplitude and decay time of sEPSCs. The 10 μM Pb 2+ depressed the inhibition of EPSCs by CCh, reduced the CCh-induced enhancement of PPF and the response to 10-Hz pulse-trains, and also affected the modulation of sEPSCs by CCh. The results suggested that the activation of muscarinic acetylcholine (ACh) receptors in hippocampus could modulate glutamatergic synaptic transmission, while Pb 2+ exposure would lead to an alteration of muscarinic modulation, which might be involved in the Pb 2+-induced impairment of synaptic transmission and plasticity during learning and memory.

Facilitation of glutamatergic synaptic transmission in hippocampal CA1 area of rats with traumatic brain injury

We investigated the effects of traumatic brain injury (TBI) on the glutamatergic synaptic transmission in the hippocampal CA1 area. A moderate impact (3.8–4.8 atm) was applied onto the left parietal cerebral cortex by a fluid percussion injury (FPI) device. Conventional intracellular recordings were made from hippocampal CA1 pyramidal neurons in vitro. Electrophysiological properties of these neurons were compared between three groups (control, FPI-ipsilateral, and FPI-contralateral). The excitability of postsynaptic membrane of CA1 pyramidal neurons was not altered by the moderate FPI; however, the evoked glutamatergic excitatory synaptic transmission in the pyramidal neurons of post-FPI-CA1 was enhanced. Paired-pulse facilitation (PPF) was significantly suppressed in both the FPI-ipsilateral and FPI-contralateral groups and the frequencies of mEPSPs in neurons from the bilateral FPI groups were greater than the frequency in the control group. These results suggest that the glutamatergic synaptic transmission in the hipppocampal CA1 area is facilitated through presynaptic mechanisms after TBI.

Modulation of 5HT1A responsiveness in CA1 pyramidal neurons by in vivo activation of corticosteroid receptors.

In this study we describe modulatory effects exerted by in vivo activation of corticosteroid receptors on 5HT responsiveness of rat CA1 pyramidal neurons. In the first series of experiments, adrenalectomized (ADX) rats were injected with corticosterone one hour prior to decapitation (1-1000 micrograms/100 g body weight) after which 5HT1A induced hyperpolarizations were determined in vitro by means of intracellular recordings. It appeared that 5HT responsiveness was dose-dependently affected by corticosterone injections: 5HT responses were relatively large when no corticosteroid receptors were activated (ADX); similar 5HT responses were observed or when both mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) were occupied by injection of high doses of corticosterone (100-1000 micrograms/100 g body weight). However, compared to the latter group, 5HT hyperpolarizations were significantly suppressed in slices from rats that received moderate amounts of corticosterone (10-30 micrograms/100 g). Next, we investigated whether physiological variations of plasma corticosterone levels as occurring in intact rats correlated with the transmitter responsiveness. It was found that high plasma levels of corticosterone due to either stress or exogenous application of high doses of corticosterone correlated with large 5HT-responses in vitro. Interestingly, the large 5HT responses recorded after stress were clearly suppressed by pretreatment with RU38486, a GR antagonist. Altogether, this study presents further evidence that 5HT transmission in hippocampal CA1 area is modulated by differential steroid receptor activation as may occur under physiological circumstances due to different plasma concentrations of corticosterone.

Workshop on animal models of traumatic brain injury.

Workshop on animal models of traumatic brain injury.