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Prolyl carboxypeptidase (PRCP), a serine protease, is widely expressed in the body including liver, lung, kidney and brain, with a variety of known substrates such as plasma prekallikrein, bradykinin, angiotensins II and III, and α-MSH, suggesting its role in the processing of tissue-specific substrates. In the brain, PRCP has been shown to inactivate hypothalamic α-MSH, thus modulating melanocortin signaling in the control of energy metabolism. While its expression pattern has been reported in the hypothalamus, little is known on the distribution of PRCP throughout the mouse brain. This study was undertaken to determine PRCP expression in the mouse brain. Radioactive in situ hybridization was performed to determine endogenous PRCP mRNA expression. In addition, using a gene-trap mouse model for PRCP deletion, X-gal staining was performed to further determine PRCP distribution. Results from both approaches showed that PRCP gene is broadly expressed in the brain.

This experiment investigated the existence of a direct anatomical connection between lateral preoptic and ventral tegmental areas that mediate brain stimulation reward using the behavioral adaptation of the collision test. This test is a double-pulse, two-electrode technique based on the axonal conduction failure that occurs when two separate sites in the same axon bundle are concurrently stimulated. This anatomical arrangement is inferred from the shape of the function relating the effectiveness of double-pulse stimulation to the interval between pulses. In this study, nine rats with a total of 44 pairs of sites were examined. In two pairs only was there a profile suggestive of an axonal collision effect, while the double-pulse effectiveness curve consistent with the properties of transynaptic collision was apparent for a single pair of sites; the remaining 93% were associated with relatively flat effectiveness curves. While electrode misalignment could be responsible for these results, there was adequate sampling to suggest that the preponderance of first stage signals that give rise to the rewarding effects mediated by the lateral preoptic and ventral tegmental areas do not travel along the same fiber bundle. However, stimulation applied to both sites concurrently produces a summation that is roughly 40% greater than stimulation at either site alone, suggesting reasonable integration of the reward signals generated by lateral preoptic and ventral tegmental area stimulation.

Given the putative role of the lateral preoptic area as a primary contributor of the cell bodies of origin of the descending pathway linking a subset of lateral hypothalamic and ventral tegmental area reward neurons, the distribution of self-stimulation sites in this structure was mapped in 22 animals using moveable electrodes and threshold procedures. Ninety-seven electrode sites were evaluated with placements ranging from just rostral to the midline convergence of the anterior commissure back to the transition zone between the lateral preoptic and lateral hypothalamic areas; of these, roughly 2/3 supported self-stimulation which was widely observed throughout the lateral preoptic area and medial forebrain bundle. In general, self-stimulation thresholds obtained from lateral sites were most stable, and progressively so approaching more caudal regions. Examination of the slopes of the period/current trade-off functions revealed a tendency for higher values in lateral and caudal sites; in contrast, dorsoventral excursions did not influence these estimates. Taken together, these data provide support for the notion that the substrate for brain-stimulation reward in the lateral preoptic area has a relatively homogeneous distribution that is more diffusely organized than that found in reward sites activated further caudally in the medial forebrain bundle.

Electrical self-stimulation in the lateral hypothalamus of both hemispheres was recorded in 14 rats before and after administration of a unilateral ibotenic acid lesion of the cell bodies in the region of the lateral preoptic area. A significant decrease in the rate of self- stimulation at each of two stimulation intensities was found when the electrode was placed in the hemisphere in which the ibotenic acid lesion was made. This decrease remained constant over 21 days of testing. No changes were detected in rate of self-stimulation in the intact contralateral hemisphere. These results provide evidence for a role in lateral hypothalamic self-stimulation of intrinsic neurons located in the region of the lateral preoptic area.

Extracellular recordings were made from single neurons in the lateral habenular nucleus of urethane-anesthetized rats. Single pulse stimulation of the entopeduncular nucleus influenced the spontaneous activity of 200 out of 293 (68%) lateral habenular neurons tested, with the most frequent response being suppression of activity and initial activation followed by suppression. Single pulse stimulation of the lateral preoptic area influenced the activity of 140 out of 165 (85%) lateral habenular neurons tested. Responses were similar to those for entopeduncular stimulation. In a series of 137 lateral habenular units, 85 (62%) were influenced by stimulation of both sites indicating convergence of inputs from these two forebrain areas. Approximately half of the lateral habenular neurons which received converging inputs from entopeduncular nucleus and lateral preoptic area were activated antidromically by stimulation of the fasciculus retroflexus, indicating that they were output neurons. These electrophysiological findings support the suggestion from recent neuroanatomical studies that the lateral habenular nucleus is a site of integration for entopenduncular and limbic inputs and in turn sends signals to the midbrain.

Extracellular recordings were obtained from neurons in the lateral habenular nucleus in urethane anesthetized rats. The following observations were made: (1) Action potentials of most neurons displayed a biphasic wave with an initial positivity. The interspike interval distributions were mostly unimodal. (2) The mean spontaneous firing rate was 9.2/sec with a range of 0–45/sec. (3) Following single pulse stimulation of the septum, 4 types of response pattern of lateral habenular neurons were observed: inhibition alone (23%), activation alone (9%), inhibition-activation sequence (21%), activation-inhibition sequence (10%). The majority of neurons were inhibited. Repetitive stimulation increased the total percentage of neurons being influenced. (4) Single and repetitive stimulation of the lateral preoptic area produced a similar effect on unit discharge of lateral habenular neurons as those of the septum. (5) In about 90% of the neurons, a strong convergence of both septal and preoptic influences was observed. Both synergistic and antagonistic effects of these two stimulations upon unit discharge of lateral habenular neurons were found. Interaction of the two stimulations was also studied. The effect of the interaction was dependent on the time interval between the two stimulations and the effect of the individual stimulation.

Previous ablation studies implicate the preoptic area as having an inhibitory influence on emotional behavior, while stimulation studies have elicited attack from the preoptic region. In the present investigation, stimulation of the medial preoptic area and a restricted, medial, portion of the lateral preoptic area elicited directed attack on a rat while periventricular preoptic stimulation elicited at most pupil dilation. Concurrent stimulation of medial or mediolateral preoptic sites, and sites in the lateral hypothalamus from which attack could be elicited, facilitated attack. Pairing periventricular preoptic with hypothalamic stimulation suppressed attack, increasing latencies during both individual hypothalamic and concurrent stimulation trials, thus having a long-term effect.

The ganglion cells of the nervus terminalis (NT cells) of the dwarf gourami could be classified into type I (giant) and type II (medium to large) cells. After unilateral application of cobaltic-lysine to the optic nerve, only the type II NT cells on the contralateral side were retrogradely labelled. The dendrites ramified near the cell bodies and invaded the olfactory bulb. The axons ran caudally, while taking dorsal and ventral courses, through the ventral telencephalon and the lateral preoptic area, and entered the optic tract.

The central nervous structures involved in febrile responses were investigated in conscious rats by means of the 2-deoxy-D-[14C]glucose autoradiographic technique. An intravenous injection of endogenous pyrogen prepared from rabbit white blood cells induced a significant rise in the rectal temperature of rats accompanied by a decrease in the skin temperature. According to autoradiographs, significant increases in metabolic activity were observed in the lateral preoptic area, posterior part of dorsomedial thalamus, posterior hypothalamus and the red nucleus during an induced fever. Because of the close relationship between metabolic activity and brain function, these regions are considered to compose the neural components directly or indirectly related with the febrile responses.

Evoked potentials to electrical stimulation of the septum and the lateral preoptic area were recorded in the lateral habenular nucleus in urethane anesthetized rats. Evoked potentials to septal stimulation consisted of 4 components: a first positive component found to be mediated by a direct pathway via the stria medullaris; a second positive component mediated by a polysynaptic pathway with fewer synapses via the stria medullaris, the anterior, the paratenial, and the dorsomedial nuclei of the thalamus; a negative and a third positive component mediated by a polysynaptic pathway via the hippocampal commissure, the dorsal hippocampus, the stria medullaris, and the anterior, the paratenial and the dorsomedial thalamic nuclei. Evoked potentials to lateral preoptic stimulation consisted also of 4 components: a first positive component was mediated by a direct pathway via the inferior thalamic peduncle and the stria medullaris, while the other 3 were mediated by a polysynaptic pathway involving the inferior thalamic peduncle, the stria medullaris, as well as the anterior, the paratenial and the dorsomedial nuclei of the thalamus.