The retrosplenial cortex has been implicated in processing sensory information and spatial learning, with abnormal neural activity reported in association with psychedelics and in mouse and non-human primate models of autism spectrum disorders (ASDs). The direct role of the retrosplenial cortex in regulating social behaviors remains unclear. In this work, we reveal that neural activity in the retrosplenial agranular cortex (RSA), a subregion of the retrosplenial cortex, is initially activated, then quickly suppressed upon social contact. This up-down phase of RSA neurons is crucial for normal social behaviors. Parvalbumin-positive GABAergic neurons in the hippocampal CA1 region were found to send inhibitory projections to the RSA. Blocking these CA1-RSA inhibitory inputs significantly impaired social behavior. Notably, enhancing the CA1-RSA inhibitory input rescued the social behavior defects in an ASD mouse model. This work suggests a neural mechanism for the salience processing of social behavior and identifies a potential target for ASD intervention using neural modulation approaches.
Animals ; Social Behavior ; CA1 Region, Hippocampal/physiology* ; Mice ; Male ; Autism Spectrum Disorder/physiopathology* ; Mice, Inbred C57BL ; GABAergic Neurons/drug effects* ; Neural Inhibition/drug effects* ; Parvalbumins/metabolism* ; Neural Pathways/physiology* ; Cerebral Cortex/physiology*

Stimulation of the trigeminal nerve can elicit various cardiovascular and autonomic responses; however, the effects of anesthesia with pentobarbital sodium on these responses are unclear. Pentobarbital sodium was infused intravenously at a nominal rate and the lingual nerve was electrically stimulated at each infusion rate. Increases in systolic blood pressure (SBP) and heart rate (HR) were evoked by lingual nerve stimulation at an infusion rate between 5 and 7 mg·kg(-1)·h(-1). This response was associated with an increase in the low-frequency band of SBP variability (SBP-LF). As the infusion rate increased to 10 mg·kg(-1)·h(-1) or more, decreases in SBP and HR were observed. This response was associated with the reduction of SBP-LF. In conclusion, lingual nerve stimulation has both sympathomimetic and sympathoinhibitory effects, depending on the depth of pentobarbital anesthesia. The reaction pattern seems to be closely related to the autonomic balance produced by pentobarbital anesthesia.
Adjuvants, Anesthesia ; administration & dosage ; pharmacology ; Adrenergic alpha-Antagonists ; pharmacology ; Animals ; Autonomic Nervous System ; drug effects ; Cats ; Dose-Response Relationship, Drug ; Electric Stimulation ; Electrocardiography ; drug effects ; Hemodynamics ; drug effects ; Hexamethonium ; pharmacology ; Hypnotics and Sedatives ; administration & dosage ; pharmacology ; Infusions, Intravenous ; Lingual Nerve ; drug effects ; physiology ; Male ; Neural Inhibition ; Phentolamine ; pharmacology ; Trigeminal Nerve ; drug effects ; physiology

OBJECTIVETo study the central role of ginkgolide B (BN52021) in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus (PVN) neurons in hypothalamic slice preparation and to elucidate the mechanism involved.

METHODSExtracellular single-unit discharge recording technique.

RESULTS(1) In response to the application of ginkgolide B (0.1, 1, 10 micromol/L; n = 27) into the perfusate for 2 min, the spontaneous discharge rates (SDR) of 26 (26/27, 96.30%) neurons were significantly decreased in a dose-dependent manner. (2) Pretreatment with L-glutamate (L-Glu, 0.2 mmol/L) led to a marked increase in the SDR of all 8 (100%) neurons in an epileptiform pattern. The increased discharges were suppressed significantly after ginkgolide B (1 micromol/L) was applied into the perfusate for 2 min. (3) In 8 neurons, perfusion of the selective L-type calcium channel agonist, Bay K 8644 (0.1 micromol/L), induced a significant increase in the discharge rates of 8 (8/8, 100%) neurons, while ginkgolide B (1 micromol/L) applied into the perfusate, could inhibit the discharges of 8 (100%) neurons. (4) In 8 neurons, the broad potassium channels blocker, tetraethylammonium (TEA, 1 mmol/L) completely blocked the inhibitory effect of ginkgolide B (1 micromol/L).

CONCLUSIONThese results suggest that ginkgolide B can inhibit the electrical activity of paraventricular neurons. The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and potentially concerned with delayed rectifier potassium channel (K(DR)).

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; pharmacology ; Action Potentials ; drug effects ; Analysis of Variance ; Animals ; Animals, Newborn ; Calcium Channel Agonists ; pharmacology ; Dose-Response Relationship, Drug ; Drug Interactions ; Fibrinolytic Agents ; pharmacology ; Ginkgolides ; pharmacology ; Glutamic Acid ; pharmacology ; In Vitro Techniques ; Lactones ; pharmacology ; Neural Inhibition ; drug effects ; Neurons ; drug effects ; Paraventricular Hypothalamic Nucleus ; cytology ; Potassium Channel Blockers ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Tetraethylammonium ; pharmacology

OBJECTIVEThe literature has shown that cognitive and emotional changes may occur after chronic treatment with glucocorticoids. This might be caused by the suppressive effect of glucocorticoids on hippocampal neurogenesis and cell proliferation. Paroxetine, a selective serotonin reuptake transporter, is a commonly used antidepressant for alleviation of signs and symptoms of clinical depression. It was discovered to promote hippocampal neurogenesis in the past few years and we wanted to investigate its interaction with glucocorticoid in this study.

METHODSAdult rats were given vehicle, corticosterone, paroxetine, or both corticosterone and paroxetine for 14 d. Cell proliferation in the dentate gyrus was quantified using 5-bromo-2-deoxyuridine (BrdU) immunohistochemistry.

RESULTSThe corticosterone treatment suppressed while paroxetine treatment increased hippocampal cell proliferation. More importantly, paroxetine treatment could reverse the suppressive effect of corticosterone on hippocampal cell proliferation.

CONCLUSIONThis may have clinic application in preventing hippocampal damage after glucocorticoid treatment.

Analysis of Variance ; Animals ; Bromodeoxyuridine ; metabolism ; Cell Count ; Cell Proliferation ; drug effects ; Corticosterone ; pharmacology ; Drug Interactions ; Hippocampus ; cytology ; Male ; Neural Inhibition ; drug effects ; Neurons ; drug effects ; Paroxetine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Serotonin Uptake Inhibitors ; pharmacology

OBJECTIVEOur previous work suggested that sensitivity of hippocampal neurons is changed in process of epileptic activities, and closely parallel to the dynamic characteristic of epileptic activity of the neurons. This study investigated the sensitivity of epileptic brain to vagal nerve stimulation (VNS) in epileptic process.

METHODSEpileptic model was evoked by penicillin. Left vagal nerves were stimulated to inhibit the seizures induced by penicillin. The electrocorticography (ECoG) and electromyography (EMG) were recorded to analyze inhibiting effect of VNS in epileptic process.

RESULTSIt was found that VNS could inhibit the seizures caused by penicillin, and the inhibiting effect of VNS to seizures increased as the vagal nerve stimulating time prolonged. It was also found that the inhibiting effect of VNS to seizures decreased in epileptic process.

CONCLUSIONThe results suggested that the sensitivity of epileptic brain to VNS was different in epileptic process. The inhibiting effect of VNS to seizure decreased as the development of seizures.

Action Potentials ; physiology ; Animals ; Electric Stimulation ; Electroencephalography ; Electromyography ; Epilepsy ; chemically induced ; prevention & control ; Frontal Lobe ; physiopathology ; Male ; Motor Cortex ; drug effects ; physiopathology ; Neural Inhibition ; physiology ; Nonlinear Dynamics ; Parietal Lobe ; physiopathology ; Penicillins ; Rats ; Rats, Sprague-Dawley ; Seizures ; chemically induced ; prevention & control ; Vagus Nerve ; physiology