Noradrenerge Modulation thermosensitiver Neurone im Hypothalamus der Ratte.

The paraventricular nucleus (PVN) and the supraoptic nucleus (SON) are the major sites of neuronal control for many homeostatic functions, such as the osmoregulation, the adjustment of the body temperature and others. Neurons of the PVN and SON receive direct input via noradrenergic afferents, the cell bodies of which originate primarily in the A2 and A6 cell groups of the medulla oblongata and locus coeruleus. We have examined the effects of the noradrenergic α1-agonist Phenylephrine (PHE) on the firing rate (FR) of neurons in slices of PVN and SON at constant temperature and during sinusoidal temperature changes. Hypothalamic brain slices (400 μm) were made from male Sprague-Dawley rats (150-250g), incubated in artificial cerebrospinal fluid (aCSF) and constantly oxygenated with 95%O2/5% CO2 at pH 7.3-7.5 and a osmolality of 295±5 mosmol kg-1. A slice was placed on a thermode in the recording chamber and superfused continuously with oxygenated aCSF. Extracellular single-unit activity was recorded using glass electrodes with a resistance of about 0.8-2.0MΩ. During recording, slices were exposed for 5-10 minutes to 2-10 μM PHE or 10 μM PHE in combination with 10 μM of the α1-antagonist Prazosin (PRA). Constant temperature or sinusoidal temperature changes (37°C±3°C, f= 0.005 Hz) was controlled via a homemade thermostimulator device. Data was acquired with homemade hard- and software and analysed with IGOR Pro (WaveMetrics). Neuronal thermosensitivity was calculated off-line by linear regression analysis of the frequency/temperature curves to determine the temperature coefficient (TC; impulses*s-1*°C-1). In response to bath application of 2-10 μM PHE, the majority (18 out of 24) of the neurons showed a significant increase in FR of up to 400% at constant temperature. In most neurons application of PHE during sinusoidal temperature (37°C±3°C, f= 0.005Hz) change, resulted in a dramatic increase in firing rate during ascending phases or close to the maximum of the temperature sinus, while the firing rate often was inhibited during descending phases close to the minimum of the temperature sinus. This PHE-induced effect was completely blocked by co-application of the α1-antagonist Prazosin. The majority of temperature-insensitive neurons showed an augmentation in thermosensitivity during PHE application (12 out of 21 neurons). In six of them, PHE administration even lead to TC-Values above 0.8 Hz/°C. The temperature-sensitivity of warmsensitive neurons were only hardly affected by PHE (n= 2) or even decreased (n= 1). In some neurons, the PHE-induced elevation of temperature sensitivity lead to an sharp ON-OFF characteristic of the firing rate during sinusoidal temperature changes. During exposure of ascending temperature the former silent neurons rapidly increased their firing rate to a plateau, from which the activity dropped to zero at a certain point of the descending temperature. Another feature of increased temperature sensitivity during PHE was a distinctive shift of the term of maximal neuronal firing rate relative to the maximum of the sinusoidal temperature course and relative of the situation prior PHE application. The mean of this temporal shift was in some of the examined neurons -36 s (SD 20.5 s, n= 7) earlier, i.e. their maximal firing rate was shifted to lower values of the ascending temperature sinus.