The pro-convulsant actions of corticotropin-releasing hormone in the hippocampus of infant rats

• Published in: Neuroscience 1998-05, Vol.84 (1), p.71-79
• Main Authors: Hollrigel, G.S., Chen, K., Baram, T.Z., Soltesz, I.
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Animals, Newborn - physiology; Biological and medical sciences; Convulsants - pharmacology; Corticotropin-Releasing Hormone - pharmacology; development; epilepsy; Evoked Potentials - physiology; excitability; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; GABA; glutamate; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - physiology; Kinetics; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Patch-Clamp Techniques; Pyramidal Cells - drug effects; Pyramidal Cells - physiology; Rats; Rats, Sprague-Dawley; seizure; Synapses - drug effects; Synapses - physiology; Synaptic Transmission - drug effects
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(97)00499-5

Whole-cell patch-clamp and extracellular field recordings were obtained from 450- μm-thick brain slices of infant rats (10–13 days postnatal) to determine the actions of corticotropin-releasing hormone on glutamate- and GABA-mediated synaptic transmission in the hippocampus. Synthetic corticotropin-releasing hormone (0.15 μM) reversibly increased the excitability of hippocampal pyramidal cells, as determined by the increase in the amplitude of the CA1 population spikes evoked by stimulation of the Schaffer collateral pathway. This increase in population spike amplitude could be prevented by the corticotropin-releasing hormone receptor antagonist α-helical (9–41)-corticotropin-releasing hormone (10 μM). Whole-cell patch-clamp recordings revealed that, in the presence of blockers of fast excitatory and inhibitory synaptic transmission, corticotropin-releasing hormone caused only a small (1–2 mV) depolarization of the resting membrane potential in CA3 pyramidal cells, and it did not significantly alter the input resistance. However, corticotropin-releasing hormone, in addition to decreasing the slow afterhyperpolarization, caused an increase in the number of action potentials per burst evoked by depolarizing current pulses. Corticotropin-releasing hormone did not significantly change the frequency, amplitude or kinetics of miniature excitatory postsynaptic currents. However, it increased the frequency of the spontaneous excitatory postsynaptic currents in CA3 pyramidal cells, without altering their amplitude and single exponential rise and decay time constants. Corticotropin-releasing hormone did not change the amplitude of the pharmacologically isolated (i.e. recorded in the presence of GABA A receptor antagonist bicuculline) excitatory postsynaptic currents in CA3 and CA1 pyramidal cells evoked by stimulation of the mossy fibers and the Schaffer collaterals, respectively. Current-clamp recordings in bicuculline-containing medium showed that, in the presence of corticotropin-releasing hormone, mossy fiber stimulation leads to large, synchronized, polysynaptically-evoked bursts of action potentials in CA3 pyramidal cells. In addition, the peptide caused a small, reversible decrease in the amplitude of the pharmacologically isolated (i.e. recorded in the presence of glutamate receptor antagonists) evoked inhibitory postsynaptic currents in CA3 pyramidal cells, but it did not significantly alter the frequency, amplitude, rise and decay time constants of spontan