The emission of 50 kHz frequency-modulated ultrasonic vocalizations (FM USVs) in rats has been associated with positive affective states, while a decrease in FM USVs has been associated with anxiety-like states. We tested the hypothesis in male Sprague-Dawley rats that FM USVs would complement measures of aversive memories (decrease in FM USVs) in a conditioned fear task in which we examined extinction or reconsolidation disruption. In Experiment 1, rats were fear conditioned using low-level footshock followed by extinction while monitoring freezing and FM USVs. In Experiment 2, rats were fear conditioned, the alpha-1 antagonist prazosin was used to disrupt reconsolidation of memory, and freezing and FM USVs were measured. Rats fear conditioned with low-level shock showed minimal freezing that rapidly extinguished, despite a persistent decrease in FM USVs throughout extinction. Prazosin reduced freezing in a memory reactivation-dependent manner as expected, but the reduction in FM USVs after fear conditioning remained decreased, suggesting that an affective component of memory was not impacted by prazosin. These findings indicate that FM USVs may be used as an index of fear- or anxiety-like memory, and their measurement could benefit pre-clinical animal models for assessing reduction of aversive memories.

1993-05-01·The Journal of Neuroscience1区 · 医学

Control of firing mode of corticotectal and corticopontine layer V burst-generating neurons by norepinephrine, acetylcholine, and 1S,3R- ACPD

1区 · 医学

Article

作者: Zhong Wang ; D. A. Mccormick

The ionic mechanisms by which the firing mode of layer V burst- generating neurons is modulated by noradrenergic, cholinergic, and glutamate metabotropic receptors were investigated with intracellular and extracellular recordings obtained in slices of guinea pig sensorimotor and primary visual cortices maintained in vitro. Extracellular and intracellular recordings revealed that a subset of layer V cells spontaneously generated bursts of three to six action potentials with an interburst frequency of 0.2–4 Hz. Depolarization of these cells with the intracellular injection of current inhibited burst firing and switched the cells to the tonic, single-spike mode of action potential generation. Intracellular recording from retrogradely labeled layer V pyramidal cells that project to either the superior colliculus or pontine nuclei revealed that a substantial portion of these are burst-generating cells. Application of norepinephrine (NE), the glutamate metabotropic receptor agonist 1S,3R-aminocyclopentane-1,3- dicarboxylic acid (ACPD), or ACh to layer V burst-generating cells resulted in depolarization and a subsequent shift in firing pattern from spontaneously bursting to single-spike activity. Pharmacological analysis of these responses indicated that they are mediated by the alpha 1-adrenoceptor for NE and the muscarinic subtype for ACh. Thus, the NE response was mimicked by the alpha-agonist phenylephrine but not by the beta-agonist isoprenaline, and was completely blocked by the alpha 1-antagonist prazosin but not by the alpha 2-antagonist yohimbine or the beta-antagonist propranolol. Finally, the ACh effect could be mimicked by the muscarinic agonist acetyl-beta-methylcholine (MCh) and was blocked by the muscarinic antagonist scopolamine. Intracellular recordings revealed that the NE-, MCh-, and ACPD-induced responses in bursting neurons are due to the direct activation of receptors on these cells, since block of synaptic transmission with local application of TTX or bath application of low [Ca2+]o and raised [Mg2+]o did not block the postsynaptic responses. Voltage-clamp analysis of the currents involved in the depolarizing responses of bursting cells revealed that activation of alpha 1-adrenergic, muscarinic, or glutamate metabotropic receptors resulted in a decrease in a potassium conductance that consisted of both a voltage-independent component and a voltage- and Ca(2+)-sensitive component. These results suggest that increased activity in noradrenergic, cholinergic, and glutamatergic pathways may control the firing mode of layer V corticotectal and corticopontine pyramidal cells by determining the resting membrane potential through modulation of both voltage-dependent and voltage-independent K+ conductances.(ABSTRACT TRUNCATED AT 400 WORDS)

1993-01-01·Acta physiologica Scandinavica. Supplementum

Duodenal bicarbonate secretion and mucosal protection. Neurohumoral influence and transport mechanisms.

Article

作者: Säfsten, B

Duodenal mucosal bicarbonate secretion (DMBS) plays an important role in the defence against acid discharged from the stomach. The secretion by duodenum immediately distal to the Brunner's glands area and devoid of pancreatic and biliary secretions, was investigated in vivo in anaesthetized Sprague-Dawley rats and in vitro in mucosae isolated from the American bullfrog. Transport mechanisms were studied in isolated rat duodenal enterocytes and identified by use of digitized microfluorometry and the fluoroprobe BCECF. Cyclic AMP production in enterocytes of villus vs. crypt origin was measured with radioimmunoassay. The benzodiazepines diazepam and Ro 15-1788 stimulated DMBS in the rat when administered intravenously or intracerebroventricularly; however, their stimulatory effect was abolished by bilateral proximal vagotomy, and they had no effect on the secretion by isolated bullfrog mucosa. It is concluded that these benzodiazepines stimulate secretion by acting upon the central nervous system and that their effects are vagally mediated. Dopamine, the catechol-O-methyl-transferase-inhibitor nitecapone, and the dopamine D1 agonist SKF-38393 all stimulated DMBS. The peripherally acting antagonist domperidone while having no influence on basal DMBS did prevent the influences of SKF-38393 and nitecapone. The alpha 1-antagonist prazosin had no such effects and the combined results suggest that DMBS is stimulated via peripheral dopamine D1 receptors. Intravenous, but not central nervous, administration of the muscarinic M1 receptor antagonists pirenzepine and telenzepine effectively stimulated DMBS; however their effectiveness was dependent on intact vagal nerves. Phentolamine, an unselective alpha-adrenergic antagonist, prevented the stimulation by pirenzepine and telenzepine and stimulation by carbachol was abolished by hexamethonium. It is concluded that peripheral nicotinergic and muscarinergic M1 receptors mediate stimulation of DMBS, in part by acting upon peripheral sympathetic ganglia. Whereas dopamine and SKF-38393 caused a time-dependent increase in the accumulation of cyclic AMP in duodenal enterocytes of crypt and villous origin, the D2 agonist quinpirole had an inhibitive influence. Crypt and villus cells differed in their respective time-courses in response to vasoactive intestinal polypeptide. Finally, Cl-/HCO3- exchange, Na+/H+ exchange and NaHCO3 cotransport were identified as membrane acid/base transport mechanisms in isolated duodenal enterocytes.

100 项与 Alpha-1 antitrypsin(Evolve Biologics, Inc.) 相关的药物交易

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