Brain Research Bulletin, Vol. 5, pp. 515-518. Printed in the U.S.A.

Slow Bursting Thermal Sensitive Neurons in the Preoptic Area of the Rabbit

CHRISTOPHER J. GORDON” AND JAMES EDWARD HEATH

~e~~r~rnen~ of Physiology and geophysics, 524 ~urrill Hull University of Illinois, Urbana, IL 61801

Received 25 March 1980

GORDON, C. J. AND J. E. HEATH. Slow bursting thermal sensitive neurons in the preoptic area of the rabbit. BRAIN RES. BULL. S(5) 515-518, 1980.-Recent data have shown the presence of some hypothalamic neurons with a slow bursting activity. This study reports the interactions of slow bursting neurons with thermore8ulato~ control in the preopticlanterior hypothalamus (POAH). Ninety-seven single units studied with direct thermal stimulation and with central injections of norepineph~ne (NE) or serotonin (S-HI’) were assessed for stow bursting activity. Twenty-one percent of the neurons had slow bursting activity patterns with frequencies ranging from 0.02-o. 10 Hz. Intraventricular or direct POAH injected monoamines frequently inhibited bursting activity during normothermia and/or PGAH thermal stimulation. Slow bursting neurons may elicit rhythmic thermoregulatory motor outputs, neurosecretion, and infraslow DC potentials in the central nervous system.

Norepinephrine Serotonin Single unit activity

SOME p~optic/anterior hy~thalamic (FQAH) neurons show a slow bursting activity in the absence of anesthetics [21,24]. The PGAH is considered a primary integrative site for temperature regulation [6,16]. Local thermal U3,201 and neurochemical stimulation [3,7] of the POAH with norepi- nephrine (NE) and 5-hydroxytrypta~ne (S-HT) can modify thermoregulato~ control. If these neurotransmitters also in- fluence the activity of slow bursting neurons, it would suggest that the neurons have a role in thermoregulatory control. This study reports the effects of intravent~c~ar and direct POAH injections of NE and 5-HT on the activity of thermally identified slow bursting neurons in the POAH of unanesthetized rabbits.

METHOD

Protocol

Male, New Zealand white rabbits were stereotaxically prepared [23] for recording single unit activity, for altering POAH temperature, and for injecting neurotropic agents ventricularly or directly into the POAH in the un- anesthetized state [9, 10, 111. The rabbits were placed in the experimental environment and allowed to accommodate 20-60 min before attempts to isolate single units were made. The electrode was lowered into the PGAH in 2-5 p steps until a single unit with a suitable signal/noise ratio was iso- Iated. Usually, basal firing rate was recorded for OS-l.0 min. Water was circulated through the thermode to clamp the POAH at a cool (34-37oC) tern~~t~e to determine the thermal characteristics of the neuron: Then NE or 5-HT (Sigma) was infused into the lateral ventricle at a rate of 30-40 ~1 over a period of lo-60 see or into the POAH at a rate of l-3 ~1 over a period of 30-60 sec. Monoamine con- centrations of 113 @g/p1 and 1.0-25.0 Lcgictl were used for the

ventricular and direct POAH injections, respectively. Gen- erally, POAH temperature was changed both before and after the monoamine injection. All recordings were made at room temperature (20-23°C). Previous the~ore~lation studies with rabbits have used hypothalamic monoamine doses of IO-20 pg [7] and ventricular monoamine doses of 20-80 E.cg [3].

Criteria for Identifying Slow Bursting Neurons

The output of the ratemeter on the polygraph sufficed for determining the bursting frequency and intrabursting interval of slow oscillating single units. A neuron was classified as a bursting unit when the integrated firing rate regularly fluc- tuated from a baseline to peak amplitude ratio of greater than 1:2. The lowest baseline value obtained was 0 impulses/ second, while other units had an interburst firing rate greater than 0.

RESULTS

T~~ermal Characteristics

Ninety-seven single neurons were isolated in 11 rabbits with 20 units displaying a regular bursting pattern during POAH cooling and/or monoamine stimulation. The mean bursting period (14.6 f 1.9 set) was always greater than the interbursting interval (<5 set). The frequency of bursting was consistent for each neural recording (0.067 2 0.006 Hz) and inversely correlated with the bursting period (r= -0.888).

14/20 units exhibited slow bursting activity during both no~othe~ia and PGAH cooling while 6/20 units fired toni- cally during normothermia and underwent slow bursting dur- ing PGAH cooling. Twenty-five percent of the bursting units

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516 GORDON AND HEATH

FIG. 1. Example of a tonic unit induced into slow bursting activity by POAH cooling. An intraventricular injection of 37 pg of NE resulted in an increased firing rate and also inhibited the cold-induced bursting.

were wan-sensitive, 35% as cold-sensitive, and 40% as thermal-insensitive. Combining the bursting and non- bursting units together (N=97), the distribution of warm-, cold-, and thermal-insensitive units was 4C%, 25%, and 35%, respectively.

Based on overa changes in firing rate, warm- and cold- sensitive units were facilitated and thermal-insensitive units inhibited by ventricular and direct POAH injections of the monoamines (Table 1). Cold-sensitive neurons were consis- tently facilitated by NE while warm-sensitive neurons were facilitated by both S-HT and NE.

There were several interactions between POAH cooling and the monoamines on the activity of slow bursting neurons. For example, five tonically active units were in- duced into bursting by POAH cooling; however, the thermally-induced bursting was inhibited by injections of NE 111 and 5-HT 141 (Fig. 1). Another form of modulating the activity of slow bursting neurons was a S-HT-induced in- crease in the rate and amplitude of bursting (Fig. 2). One thermal-insensitive neuron with a relatively slow bursting frequency was converted to a rapid bursting unit by a direct POAH injection of NE (Fig. 3).

DISCUSSION

In spite of the few number of units reported in this study, the novel interactions between slow bursting neurons and temperature-active neurotransmitters merits postulating on the role of these neurons in thermoregulation. Primarily, the conversion of a unit from tonic to slow bursting by POAH cooling implicates these neurons in the processing of thermal info~ation, For example, a pulsed rather than tonic signal may be an effective neural code for detecting a decrease in POAH temperature. In addition, the antagonism between cold-induced bursting and the monoamine neurotransmitters also represents a form of thermal control. Past studies using anesthetized animals have shown that NE and S-HT specifi-

TABLE I OVERALL SHIFTS IN FIRING RATE OF SLOW BURSTING NEURONS

TO INTRAVENTRICULAR AND DIRECT POAH INJECTIONS OF NOREPINEPHRINE (NE) AND 5-HYDROXYTRYmAMINE (5-HT)

-

Number of units Warm- Cold-

sensitive sensitive Thermal-

insensitive

Inhibited by NE 0 0 5 Facilitated by NE 2 4 1

Inhibited by S-HT 0 1 2 Facilitated by 5-HT 3 0 0

tally facilitate or inhibit thermal sensitive neurons in the POAH [17,19]. In this study, there were some inconsisten- cies of the monoamines on the overall firing rate of thermal- sensitive neurons; however, the neurotransmitters were ef- fective in modulating patterns of slow bursting neurons.

There are several possible roles for slow bursting neurons in thermoregulatory control. Recent studies in the hypothalamo-hypophyseal system have demonstrated that slow bursting activity may be a property of neurosecretory neurons. Grouping neuron discharges into bursts may enhance the release of vasopressin from nerve terminals in the posterior hypophysis [I. Neurosecretory ceils in the su- praoptic nucleus generally have slow bursting activity 18,121. The bursting units recorded in this study may activate neurosecretion. For example, POAH cooling rapidly in- creases thyroid activity [2]. In addition, hypothalamic ther- moreceptors may also influence the release of vasopressin [ 15,221. The conversion of POAH units from tonic to phasic activity could be associated with temperature regulatory- neurosecretory activity.

Von Euler [25] first described rhythmic, temperature- sensitive voltage fluctuations in the hypothalamus of anesthetized cats with frequencies similar to some of the bursting units found in this study. Similar “infraslow” DC

RABBIT SLOW BURSTING PREOFl-IC NEURONS 517

FIG. 2. Photographic record of a single unit under normothermic conditions before (A) and 12 minutes after (B) an intraventricular injection of 24 p.g of 5-HT. Calibration mark-500 pV vs 5000 msec.

FIG. 3. Conversion from slow to rapid bursting of a thermal-insensitive neuron with a direct PGAH injection of 10.5 /~g of NE. Prior to the NE injection there was a gradual increase in unit activity, but not apparently related to PGAH temperature. After NE administration, the amplitude of bursting is reduced during PGAH cooling (CP).

518 GORDONANDHEATH

potential fluctuations have been described in various levels of the central nervous system [I]. Jahns and Werner [18] found that some POAH units recorded in anesthetized rats had thermally-induced rhythmic firing patterns. They suggested that a transition from a tonic to phasic activity state of a single unit could lead to the desynchronization of an EEG pattern. Furthermore, while mild warming of the hypothalamus leads to EEG synchronization, excessive heating promotes desynchronization of the EEG [26]. Hence, the activity of slow bursting neurons may be related to the thermally-induced changes in the brainstem electrical activity discovered in previous investigations [25,26].

Slow bursting neurons may be important in eliciting ther- moregulatory motor responses. Measuring finger tip blood flow in humans, Burton [4] found a slow rhythmic fluctuation of peripheral blood flow ranging in frequency from 0.03-o. 1 Hz superimposed on the systolic-diastolic flow pulse. Fur- thermore, ambient thermal stimulation altered the frequency of rhythmic blood flow 151. The frequency of the blood flow

rhythm is similar to oscillating changes, in blood pressure in the rabbit [27]. Interestingly, in one pathological case, a pa- tient lacking rhythmic peripheral blood flow also had a poor ability to maintain normal body temperature under thermal stress [5].

Slow oscillations in blood flow lead to similar fluctuations in skin temperature. Since heat loss to the environment can fluctuate unpredictably, it has been argued that a liner regu- lation of heat loss is accomplished with a rhythmic rather than overdamped control of skin temperature [S]. Hence, Burton and Taylor [5] proposed that there must be a neural locus in the brainstem which generates a relatively slow periodic impulse pattern for eliciting control over peripheral blood flow. Because the rhythmic activity of many POAH units can be altered by the same combinations of neuro- transmitters and thermal stimulation which lead to changes in peripheral and deep body temperature [7,20], the slow bursting neurons may likely be a part of thermoregulatory control.

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