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I Mandelbrod

Publications and source records attributed to I Mandelbrod.

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Mediobasal hypothalamic neurons are excited by the iontophoretic application of sodium.

In the course of studies on the responsiveness of mediobasal hypothalamic neurons to the iontophoretic application of cortisol, it was found that positive currents applied to a sodium chloride (1 M) barrel alone, but not to a choline chloride (1 M) barrel, frequently increased the firing of these neurons. Subsequently, systematic examination demonstrated that out of 102 MBH neurons 52 (51%) increased their firing by at least 30% with application of NaCl, using currents no greater than 10 nA. No such effect was obtained in response to Na application from a dilute solution (0.05 or 0.1 M). When glutamate was absent from the electrodes, the incidence of Na+ sensitivity fell to 17%, despite the routine use of backing currents to the glutamate barrel. K+ ions were more active than Na+ ions in producing excitation. When Na+ sensitivity was found, however, Na+ effects were produced by currents greater than K+ currents producing equivalent excitation. Like glutamate, K+ ions were capable of greatly enhancing responses to Na+. Comparison was made between cortisol and Na+ sensitivity in 70 MBH neurons; 28 cells responded to both, and 24 of them were inhibited by cortisol. Thus Na+ sensitivity is a frequent characteristic of MBH neurons inhibited by cortisol, and was present in 83% of cortisol-sensitive cells in this region. Iontophoresis of Na+ is commonly used as a control in pharmacological studies of the nervous system. Even more common is the case of concentrated NaCl solutions for recording. These procedures may not be as inert as previously thought, particularly in the hypothalamus.

Animals↗

The effects of iontophoretic application of putative neurotransmitters on the electrical activity of rat mediobasal hypothalamic neurons in relation to their steroid sensitivity.

In order to characterize the neurons responsible for ACTH release and the suppression produced by adrenocortical steroids, we have studied the pharmacological sensitivity of neurons in the region containing the highest concentration of corticotropin releasing factor (CRF) in the brain and probably responsible for most of these activities. The effects of 8 putative neurotransmitters applied iontophoretically to more than 400 mediobasal hypothalamic (MBH) neurons in the rat were examined, and compared with cortisol sensitivity of the same neurons. Glutamate was the only agent that produced excitation exclusively, while GABA, serotonin, glycine and dopamine were inhibitory in action. Mixed excitation and inhibition were produced by histamine, acetylcholine (ACh) and norepinephrine (NE). All 8 cells excited by ACh were inhibited by cortisol and constitute only about 10% of neurons sampled; these neurons are considered to be strong candidates for CRF-releasing cells. On 7 of these neurons histamine was strongly excitatory and its action greatly outlasted the iontophoretic application. Histamine, however, excited many other neurons, including those neither excited by ACh nor steroids.

Acetylcholine↗

Modification of responses to sensory and hippocampal stimuli in neurons of the rat mediobasal hypothalamus in the presence of iontophoretically applied cortisol.

The effects of iontophoretic cortisol on evoked activity was studied in rat tuberal hypothalamic units. Evoked activity from visual, auditory, sciatic nerve and hippocampal stimulation was examined in same neurons both before and during local cortisol administration. Hippocampal stimuli were studied in isolation and as conditioning stimuli for one of the sensory modalities. A constant background glutamate current was frequently used in order to shorten observation periods and to enhance inhibition of firing. Even though the predominant effect of cortisol on spontaneous firing was to reduce the firing rate, the effect of the hormone on evoked responses of all kinds was to reduce the size of the response, independent of sign, and even to reverse the nature of the response, from control facilitation to inhibition or from control inhibition to facilitation. Evoked responses in many units whose spontaneous activity was not affected by cortisol were altered by hormone. Of particular interest are a group of cells which are normally silent and respond to afferent stimulation with inhibition. The responses in these cells are reduced or changed to excitation in the inhibition. The responses in these cells are reduced or changed to excitation in the presence of cortisol and they may represent local inhibitory interneurons. The findings are related to the negative feedback of adrenocorticosteroids on CRF and ACTH release.

Animals↗