Jiro Iwata

Cardiovascular responses elicited by stimulation of neurons in the central amygdaloid nucleus in awake but not anesthetized rats resemble conditioned emotional responses

Cardiovascular responses elicited by electrical stimulation of the central amygdaloid nucleus were examined in awake and anesthetized rats. Stimulation through chronically implanted electrodes evoked increases in arterial pressure and heart rate in awake, freely behaving rats. The responses, which were dependent upon the frequency and the intensity of the stimulus, were not consistently related to the presence of evoked amygdaloid afterdischarges or to evoked behavioral reactions. Following induction of anesthesia, stimuli delivered to the same rats through the same fixed electrodes produced decreases in blood pressure and heart rate. Microinjection of L-glutamate into the amygdala of freely behaving rats also elicited increases in arterial pressure and heart rate, indicating that the cardiovascular changes evoked by electrical stimuli are due to excitation of local neurons rather than fibers of passage. The timing and pattern of the response elicited by electrical stimulation of the amygdala in the awake but not the anesthetized rat closely corresponds with that evoked by an acoustic conditioned emotional stimulus.

Interruption of projections from the medial geniculate body to an archi-neostriatal field disrupts the classical conditioning of emotional responses to acoustic stimuli.

We have previously found that the coupling of changes in autonomic activity and emotional behavior to acoustic stimuli through classical fear conditioning survives bilateral ablation of auditory cortex but is disrupted by bilateral lesions of the medial geniculate nucleus or inferior colliculus in rats. Auditory fear conditioning thus appears to be mediated by the relay of acoustic input from the medial geniculate nucleus to subcortical rather than cortical targets. Since the medial geniculate nucleus projects, in addition to auditory cortex, to a striatal field, involving portions of the posterior neostriatum and underlying archistriatum (amygdala), we have sought to determine whether interruption of connections linking the medial geniculate nucleus to this subcortical field also disrupts conditioning. The conditioned emotional response model studied included the measurement of increases in mean arterial pressure and heart rate and the suppression of exploratory activity and drinking by the acoustic conditioned stimulus following delayed classical conditioning, where the footshock unconditioned stimulus appeared at the end of the conditioned stimulus. The peak increase in arterial pressure and the duration of activity and drinking suppression were greater in unoperated animals subjected to delayed conditioning than in pseudoconditioned controls, where the footshock was randomly rather than systematically related to the acoustic stimulus. Increases in heart rate, however, did not differ in conditioned and pseudoconditioned groups. While the arterial pressure and behavioral responses therefore reflect associative conditioning, the heart rate response does not. Rats were prepared with bilateral lesions of the medial geniculate nucleus, bilateral lesions of the striatal field or asymmetrical unilateral lesions destroying the medial geniculate nucleus on one side and the striatal field on the contralateral side. The latter preparation leaves one medial geniculate nucleus and one striatal field intact but disconnected and thus produces a selective auditory deafferentation of the intact striatal field. Control groups included animals with unilateral lesion of the medial geniculate nucleus, with unilateral lesion of the medial geniculate nucleus combined with lesion of the ipsilateral striatal field, unilateral lesion of the medial geniculate combined with lesion of the contralateral anterior neostriatum (a striatal area outside of the medial geniculate nucleus projection field).(ABSTRACT TRUNCATED AT 400 WORDS)

Dissociation of associative and nonassociative concomitants of classical fear conditioning in the freely behaving rat.

An acoustic stimulus previously paired with footshock elicits stereotyped increases in arterial pressure and heart rate and induces freezing behavior in freely behaving rats. Although the arterial pressure and freezing responses differ between groups given paired and random presentations of the tone and shock, the increases in heart rate do not. These observations, if taken at face value, suggest that the arterial pressure and freezing responses reflect associative learning but that the heart rate change is a nonassociative or a pseudoconditioned response. In this article we describe three experiments aimed at determining why the CS elicits similar increases in heart rate in groups given paired and random training. The first study demonstrates that regardless of the pseudoconditioning control procedure used (random, backwards, shock-alone, or naive), the same pattern of results is obtained: the increases in arterial pressure are greater in the paired than in each control group, but the heart rate rises to the same extent in all groups. The second study determined that the context in which the responses are tested (conditioning apparatus vs. novel test chamber) does not affect the general pattern of results obtained. The third study demonstrates that the superficially similar increases in heart rate in conditioned and pseudoconditioned rats are achieved by different physiological mechanisms: coactivation of the sympathetic and parasympathetic nervous systems in conditioned rats and sympathetic excitation alone in pseudoconditioned rats. Thus, the heart is influenced by associative emotional processes, but heart rate is not, under these conditions, a particularly useful index of those influences.

Disruption of auditory but not visual learning by destruction of intrinsic neurons in the rat medial geniculate body

The contribution of intrinsic neurons in the medial geniculate body (MG) of the rat to the classical conditioning of emotional responses to acoustic stimuli was examined. Injection of ibotenic acid, which destroys cell bodies but not axons of passage, into the MG disrupted the conditioned changes in mean arterial pressure and emotional behavior elicited by a tone previously associated with footshock. Unconditioned responses elicited by the tone and by the footshock were unaffected. Moreover, the same animals readily learned to associate a visual stimulus with footshock. Thus, destruction of intrinsic neurons in the MG selectively disrupts the conditioning of emotional responses to acoustic stimuli. The MG appears to be the afferent link in a modality specific emotional learning pathway.

Destruction of intrinsic neurons in the lateral hypothalamus disrupts the classical conditioning of autonomic but not behavioral emotional responses in the rat

The present study examined whether destruction of intrinsic neurons in the lateral hypothalamus of the rat would disrupt the acquisition of classically conditioned changes in arterial pressure. Ibotenic acid, a cellular toxin which spares axons of passage, was injected bilaterally in the hypothalamus either medial or lateral to the fornix. After 2 weeks the animals were subjected to classical fear conditioning trials involving the presentation of a tone in association with footshock. The next day changes in arterial pressure and emotional behavior elicited by the tone alone were measured. Destruction of intrinsic neurons in the lateral hypothalamus prevented the normal establishment of the arterial pressure conditioned response but did not affect the behavioral response. Unconditioned arterial pressure responses elicited by the tone and shock were not affected. Medial hypothalamic injections had no effect on any of the responses. The location of the lateral hypothalamic cell loss overlapped with the neurons projecting to the autonomic region of the spinal cord. Intrinsic neurons in the lateral hypothalamus therefore appear to be specifically involved in mediating learned cardiovascular adjustments.

Sodium sensitivity of blood pressure and baroreceptor reflex function in patients with essential hypertension.

In order to define the role of the baroreceptor reflex function in the sodium sensitivity of blood pressure in patients with mild essential hypertension, 25 patients were classified into two groups, salt-sensitive and salt-insensitive, depending on the difference in the averages of the resting systolic blood pressure, taken hourly on the fifth day of 7 days of sodium depletion and on the fifth day of 7 days of repletion. Increases in urinary sodium excretion and body weight and a decrease in haemotocrit during the sodium repletion period were similar in both groups. Baroreceptor reflex function, estimated from the baroreceptor slope and the blood pressure change on a 70° tilting test, was enhanced by the sodium repletion period in the sodium-insensitive group but not in the sodium-sensitive group. These results suggest that sodium sensitivity might be due to differences in the ability of the baroreceptor reflex function to become sensitized during a high sodium intake.