Yutaka Oomura

Central control of sexual behavior

Neuronal activity changes in the medial preoptic area (MPOA) of the male monkey were related to the commencement of sexual behavior, penile erection and the refractory period following ejaculation. Similarly, changes in the female MPOA were related to the commencement of sexual behavior and presentation. Increased neuronal activity in the dorsomedial hypothalamic nucleus (DMH) in the male monkey and in the ventromedial hypothalamic nucleus (VMH) in the female monkey was synchronized to each mating act. Stimulation study and neuronal activity recordings in the MPOA, DMH and VMH suggest involvement of MPOA neurons in sexual arousal, and of male DMH and female VMH neurons in the copulatory act. Stimulation experiment on the various parts in the hypothalamus of the female monkey also supports the conclusion.

Neuron activity of the ventromedial hypothalamus and the medial preoptic area of the female monkey during sexual behavior

To elucidate the neural mechanisms of the sexual behavior of the female monkey, single neuron activity of the ventromedial hypothalamus (VMH) and the medial preoptic area (MPOA) was recorded during sexual behavior with a male partner. Copulation was initiated when either the males touch elicited passive presenting (receptive presenting) or when the females active presenting (proceptive presenting) evoked mounting from the male. Proceptive presenting with no mating acts evoked activity changes in about 40% of cells in the VMH (mainly excitation) and MPOA (mainly inhibition). When the males mating acts were manifested, 56% of VMH cells and 87% of MPOA cells showed firing changes during presenting, with the proportion of MPOA cells which showed excitation significantly increased. Progress of mating acts of the male partner (e.g. increases in the rate and/or number of thrusting), enhanced activity changes in about 40% of VMH and 70% of MPOA cells tested. The findings suggest that VMH and MPOA cells are involved in the control of sexual behavior in different ways: excitation of the VMH and inhibition of MPOA are related to execution of presenting, while excitation of MPOA is related to sexual intercourse with a male partner; and mating acts of a male partner modulate activity of both VMH and MPOA neurons of the female.

Olfactory coding in the monkey lateral hypothalamus: Behavioral and neurochemical properties of odor-responding neurons

The activity of glucose-sensitive (GS) and glucose-insensitive (GIS) neurons was recorded in the lateral hypothalamic area (LHA) of monkeys during olfactory stimulation, a conditioned alimentary bar press task, and microelectrophoretic application of catecholamines. Olfactory stimuli evoked response of 88% of the GS neurons, and 52% of the GIS cells responded to odors. The GS neurons were more broadly tuned across odorants than the GIS cells, and their responses to various smells with distinct hedonic value were also differential. The odor-responding GS neurons were depressed during the bar press and reward periods of the task, and were mainly inhibited by dopamine. The odor-responding GIS cell activity increased in response to cue light and tone, and was facilitated by dopamine. Histological examinations disclosed topographic dissociation of the odor-responding GS and GIS cells: the former were located in more ventromedial regions than the latter. The results indicate that the GS neurons integrate multiple chemosensory inputs from both endogenous and exogenous sources in the regulation of feeding: whereas the GIS cells distinguish among fewer, more specific cues to control food acquisition behavior.

Complex attributes of lateral hypothalamic neurons in the regulation of feeding of alert rhesus monkeys

To elucidate the roles of glucose-sensitive (GS) and glucose-insensitive (GIS) cells of the lateral hypothalamic area (LHA), single neuron activity was recorded during 1) microelectrophoretic administration of chemicals, 2) a conditioned bar press feeding task, 3) gustatory, 4) olfactory, and 5) electrical brain stimulation. GS and GIS neurons showed different firing rate changes during phases of the task, and the responses were highly influenced by the palatability of the food and the motivational (hunger or satiety) state of the animal. The two groups of cells also differed in their responsiveness to gustatory and olfactory stimuli: GS neurons were more likely to respond to tastes and odors than GIS cells. Taste- and odor-responsive GS neurons were primarily suppressed by electrophoretically applied noradrenaline and were localized ventromedially within the LHA. The chemosensitive GIS cells, being organized along a dorsolateral axis, were especially excited by dopamine. The two sets of neurons had distinct connections with associative (orbitofrontal, prefrontal) cortical areas. GS and GIS cells, thus, appear to have differential and complex attributes in the control of feeding.

Taste and olfactory modulation of feeding related neurons in behaving monkey

Single neuron activity in the monkey lateral hypothalamus (LHA) was recorded by multibarreled electrode during a bar press feeding task. Activity of glucose-sensitive (GS) neurons decreased during bar press (BP) and reward (RW) periods. The inhibition was caused by activation of beta-adrenoceptors and opioid receptors respectively. Glucose-insensitive (GIS) neurons were excited during BP and RW, and at cue light (CL). Excitation at CL and BP was caused by activation of dopaminergic receptors. Among GS neurons, 66% responded to taste and 88% to odor. These responses were 39% and 52% in GIS neurons. GS neurons responded predominantly to two or more taste and odor stimuli while GIS neurons responded to only one stimulant. GS neurons have dense mutual connections with the prefrontal area, and GIS neurons are connected with the motor area. Gustatory and olfactory stimulation elicited responses in 67% of GS neurons and in only 21% of GIS neurons. Data suggest that GS and GIS neurons may have different functions in feeding: GS neurons process endogenous chemical information and integrated chemical sensations, and GIS neurons process external information processing, motor control and discriminative chemical sensations.

Functional heterogeneity of the monkey lateral hypothalamus in the control of feeding

Regional differences in the effects of electrical (ES) and chemical stimulation on execution of a bar-press feeding task, and in neuronal activity related to feeding, glucose sensitivity, and odor responsiveness were examined in the lateral hypothalamic area (LHA) of monkeys. In satiated animals, ES of the far lateral and ventral LHA induced bar-press feeding. In hungry animals, ES of the dorsal LHA suppressed the feeding task only during the stimulation period, but prolonged feeding suppression that occurred after ES of the ventromedial LHA. Microinjection of Na-glutamate into LHA sites where ES was effective in suppressing feeding had no effect, but it was effective in the medial hypothalamus. Glucose-sensitive (GS) neurons decreased in activity during bar pressing and/or during the ingestion period. Glucose-insensitive (GIS) neurons showed a cue-related excitation more often than GS neurons. Odor-responding GS and GIS cells were localized in ventromedial and lateral LHA sites, respectively. The present study suggests the regional heterogeneity of the LHA in feeding regulation, depending on both hunger and satiety states.

Proceptive presenting elicited by electrical stimulation of the female monkey hypothalamus.

Proceptive presenting by female macaque monkeys was evoked by electrical stimulation of the ventromedial hypothalamic nucleus and the medial preoptic area, under conditions of partial restraint while sitting in a primate chair. This behavior could be elicited only when a male monkey was in close proximity and not when he was removed or was replaced with a female monkey or the human experimenter. This seems to be the first report on the effects of electrical brain stimulation on proceptivity in the female monkey.

Influence of acetylcholine on neuronal activity of monkey amygdala during bar press feeding behavior

Single neuron activity in the monkey amygdala was investigated during cue signalled conditioned bar press feeding behavior and the effects of electrophoretically applied acetylcholine (ACh) and atropine were analyzed. ACh increased the firing rate of one third of the neurons tested; these excitatory responses were inhibited by the muscarinic receptor antagonist atropine. No characteristic location of ACh-sensitive neurons was found, cells were diffusely distributed throughout the amygdala. Activity of ACh-sensitive neurons did not correlate with any particular event during the bar press feeding task. However, continuous application of ACh at low current intensity during the task significantly enhanced the task-related excitatory firing patterns, or markedly attenuated the inhibitory responses. Continuous application of atropine elicited or enhanced inhibitory response patterns. These results suggest that the cholinergic system of the monkey amygdala facilitates neuronal excitation but attenuates inhibition related to various phases of feeding behavior, such as to cue recognition, food aquisition and rewarding process.

Electrical stimulation of male monkey's midbrain elicits components of sexual behavior

We electrically stimulated the midbrain of male rhesus monkeys seated in a restraint chair facing the female partners and examined whether sexual behavior could be induced. When the midbrain was stimulated (0.2 ms, 50-500 microA and 50 Hz for 2.5 s), the male monkey touched and held the waist of his partner (latency; 0.9 +/- 0.4 s, mean +/- SD, n = 225), and then mounted her when she responded with presenting her hip toward him. However, this mounting, unlike when the hypothalamus was stimulated, did not lead to thrusting or ejaculation even if the stimulation continued. The sites in the midbrain where the stimulation elicited touching and mounting were the ventral tegmental area, the substantia nigra, the nucleus reticularis mesencephali and the nucleus reticularis pontis oralis et caudalis. Touching and mounting were not elicited when the partner was put away from the male or replaced by submissive male monkeys or humans. The findings suggest that the stimulation-evoked touching and mounting are components of copulatory behavior and that the midbrain structures may be involved in the sexual behavior of male monkeys.

Effects of behaviorally rewarding hypothalamic electrical stimulation on intracellularly recorded neuronal activity in the motor cortex of awake monkeys.

Effects of hypothalamic stimulation (HS) were studied in intracellular recordings obtained from 125 neurons of the motor cortex (MC). HS that was effective in reinforcing bar-press behavior, i.e. satisfactory for intracranial self-stimulation (ICSS), evoked short-latency (less than 3 ms) activation of these cortical neurons more frequently (42% of cells tested) than did HS that was ineffective in reinforcing bar-press behavior (7% of cells tested). Longer latency activation (greater than 3 ms) and inhibition (of variable onset) also occurred, but their incidence was not significantly different when HS was effective or ineffective in producing ICSS. Effects of HS that was effective in producing ICSS were also examined in 23 cells in which the spikes were followed by afterhyperpolarization (AHP) of 1.4-10 mV amplitude and 1.7-54 ms duration. The amplitudes of AHPs of greater than 8 ms duration were reduced after presentations of HSs that were effective as a reinforcer for ICSS. These results suggest that: (1) MC neurons receive reward-related hypothalamic information through pathways sufficiently direct to produce short-latency activation; and (2) a modulation of spike afterhyperpolarization can be observed in conjunction with reception of this information.