Extra-hypothalamic afferent inputs to the supraoptic nucleus area of the rat as determined by retrograde and anterograde tracing techniques

To detect neuronal cell bodies whose axon projects to the hypothalamic supraoptic nucleus, small volumes (10-50 nl) of 30% horseradish peroxidase or 2% fast blue solutions were pressure-injected into the area of one supraoptic nucleus of rats. Both dorsal and ventral approaches to the nucleus were used. In animals where the injection site extended beyond the limits of the supraoptic nucleus, retrogradely labelled cell bodies were found in many areas of the brain, mainly in the septum, the nucleus of the diagonal band of Broca and ventral subiculum in the limbic system; the dorsal raphe nucleus, the locus coeruleus, the nucleus of the dorsal tegmentum, the dorsal parabrachial nucleus, the nucleus of the solitary tract and the catecholaminergic A1 region in the brain stem; in the subfornical organ and the organum vasculosum of the lamina terminalis, as well as in the median preoptic nucleus. In contrast, when the site of injection was apparently restricted to the supraoptic nucleus, labelling was only clearcut in the two circumventricular organs, the median preoptic nucleus, the nucleus of the solitary tract and the A1 region. Injections of wheat germ agglutinin coupled with horseradish peroxidase (60-80 nl of a 2.5% solution) made in the septum and in the ventral subiculum anterogradely labelled fibers coursing in an area immediately adjacent to the supraoptic nucleus but not within it. In contrast, labelling within the nucleus was found following anterograde transport of tracer deposited in the A1 region and in an area that includes the nucleus of the solitary tract. Neurones located in the perinuclear area were densely labelled by small injections into the supraoptic nucleus; they may represent a relay station for some afferent inputs to the supraoptic nucleus. These results suggest that the supraoptic nucleus is influenced by the same brain areas which project to its companion within the magnocellular system, the paraventricular nucleus.     

Excitation of units in the lateral geniculate and contiguous nuclei of the cat by stretch of extrinsic ocular muscles

Summary In cats, anaesthetized with chloralose and paralysed, the responses of units in the right lateral thalamus were recorded while the extrinsic ocular muscles (EOM) of the right eye were stretched in the dark. Phasic responses were found in all layers of the dorsal lateral geniculate nucleus (LGNd) and in the perigeniculate nucleus (PGN). A given unit usually responded to stretch of more than one EOM and thus to more than one direction of rotation of the eye in the orbit. LGNd. Of a sample of 76 units in LGNd, 55 (72%) gave visual but no muscle responses and 21 (28%) responded to EOM stretch. In all, 40 units with EOM responses were examined and 25 of the 27 tested (93%) also had visual responses. Of the 40 units, 32 could be allocated to layers, thus: layer A, 8 (25%); layer A1, 20 (63%); layer B, 3 (9%); central interlaminar nucleus, 1 (3%). It is interesting that most of the EOM responses were found in layer A1 which receives the excitatory visual input from the eye whose EOM were stretched. Muscle responsive units occurred with ON- and OFF-centre visual responses of sustained and transient types. PGN. In PGN, 21 units gave EOM responses and most of them were also excited by visual input.The conclusion is that the LGNd and PGN recieve an extraretinal proprioceptive signal which should be present during at least large saccadic eye movements. The anatomical pathways which may be involved and the significance of the signal are discussed briefly.     

Orexin A mediation of time spent moving in rats: Neural mechanisms

The brain regulates energy balance and spontaneous physical activity, including both small- and large-motor activities. Neural mediators of spontaneous physical activity are currently undefined, although the amount of time spent in sedentary positions versus standing and ambulating may be important in the energetics of human obesity. Orexin A, a neuropeptide produced in caudal hypothalamic areas and projecting throughout the neuraxis, enhances arousal and spontaneous physical activity. To test the hypothesis that orexin A affects the amount of time spent moving, we injected orexin A (0–1000 pmol) into three orexin projection sites in male Sprague–Dawley rats: hypothalamic paraventricular nucleus, rostral lateral hypothalamic area and substantia nigra pars compacta, and measured spontaneous physical activity. Orexin A affects local GABA release and we co-injected orexin A with a GABA agonist, muscimol, in each brain site. Dopamine signaling is important to substantia nigra function and so we also co-injected a dopamine 1 receptor antagonist (SCH 23390) in the substantia nigra pars compacta. In all brain sites orexin A significantly increased time spent vertical and ambulating. Muscimol significantly and dose-dependently inhibited orexin A effects on time spent moving only when administered to the rostral lateral hypothalamic area. In the substantia nigra pars compacta, SCH 23390 completely blocked orexin A–induced ambulation. These data indicate that orexin A influences time spent moving, in three brain sites utilizing separate signaling mechanisms. That orexin A modulation of spontaneous physical activity occurs in brain areas with multiple roles indicates generalization across brain site, and may reflect a fundamental mechanism for enhancing activity levels. This potential for conferring physical activity stimulation may be useful for inducing shifts in time spent moving, which has important implications for obesity.     

The paraventricular nucleus of hypothalamus mediates the pressor response to noradrenergic stimulation of the medial prefrontal cortex in unanesthetized rats

The medial prefrontal cortex (MPFC) is a structure that is also involved in cardiovascular modulation. The injection of norepinephrine (NE) into the prelimbic (PL) area of the MPFC of unanesthetized rats evokes a pressor response which is mediated by acute vasopressin release. Vasopressin is synthesized by magnocellular cells of the paraventricular (PVN) and supraoptic nucleus (SON) of the hypothalamus. In the present study, we endeavored to determine which vasopressin-synthesizing hypothalamic nucleus is involved in the pressor pathway activated after NE injection into the PL area of the MPFC. We report here that lidocaine microinjection into the SON did not change the pressor response evoked by NE injection into the PL. However, the response to NE was blocked by prior injection of lidocaine or CoCl₂ into the PVN, indicating that this area is responsible for the mediation of this pressor response. A neuroanatomic experiment in which the neuronal tracer biotinylated dextran amine (BDA) was microinjected into the MPFC showed a lack of axons or neuronal cell bodies in the PVN, indicating that there are no direct connections between the PL area of the MPFC and the PVN. The results suggest that the PVN is involved in the mediation of the pressor response to NE in the PL area and that this pathway must relay in other brain structures before reaching the PVN.     

Histamine excites GABAergic cells in the rat substantia nigra and ventral tegmental area in vitro

We have investigated the effect of histamine (HA) on spontaneous firing of dopaminergic (DA) and GABAergic neurons in the substantia nigra (SN) and the ventral tegmental area (VTA) of the rat in vitro. Single-unit extracellular recordings were obtained and drugs were bath applied. In both regions application of HA (10 and 100 μM) did not affect the firing frequency of DAergic cells, but increased the firing of GABAergic neurons. The histamine-induced excitation was blocked by the H₁ receptor antagonist mepyramine (1 μM), but was unaffected by application of the H₂ antagonist cimetidine (50 μM) or the H₃ antagonist thioperamide (10 μM). Our results suggest that histamine does not directly inhibit dopaminergic neurons in SN and VTA, but rather that this inhibition is mediated through histamine-induced excitation of GABAergic neurons.     

Cerebellar involvement in the coordination control of the oculo-manual tracking system: effects of cerebellar dentate nucleus lesion

Summary When the hand of the observer is used as a visual target, oculomotor performance evaluated in terms of tracking accuracy, delay and maximal ocular velocity is higher than when the subject tracks a visual target presented on a screen. The coordination control exerted by the motor system of the arm on the oculomotor system has two sources: the transfer of kinaesthetic information originating in the arm which increases the mutual coupling between the arm and the eyes and information from the arm movement efferent copy which synchronizes the motor activities of both subsystems (Gauthier et al. 1988; Gauthier and Mussa-Ivaldi 1988). We investigated the involvement of the cerebellum in coordination control during a visuo-oculo-manual tracking task. Experiments were conducted on baboons trained to track visual targets with the eyes and/or the hand. The role of the cerebellum was determined by comparing tracking performance defined in terms of delay, accuracy (position or velocity tracking errors) and maximal velocity, before and after lesioning the cerebellar dentate nucleus. Results showed that in the intact animal, ocular tracking was more saccadic when the monkey followed an external target than when it moved the target with its hand. After lesioning, eye-alone tracking of a visual target as well as eye-and-hand-tracking with the hand contralateral to the lesion was little if at all affected. Conversely, ocular tracking of the hand ipsilateral to the lesion side became more saccadic and the correlation between eye and hand movement decreased considerably while the delay between target and eyes increased. In normal animals, the delay between the eyes and the hand was close to zero, and maximal smooth pursuit velocity was around 100 degrees per second with close to unity gain; in eye-alone tracking the delay and maximal smooth pursuit velocity were 200 ms and 50 deg per second, respectively. After lesioning, delay and maximum velocity were respecttively around 210 ms and 40 deg per second, that is close to the values measured in eye-alone tracking. Thus, after dentate lesioning, the oculomotor system was unable to use information from the motor system of the arm to enhance its performance. We conclude that the cerebellum is involved in the coordination control between the oculomotor and manual motor systems in visuo-oculo-manual tracking tasks.     

Changes in amphetamine stereotypy in cats after electrical stimulation of the caudate nucleus

Two types of behavioral changes arise in cats after repetitive low-frequency stimulation of the head of the caudate nucleus in cats. Behavioral inhibition is more frequently triggered from the dorsomedial zone of the head, whereas activation phenomena precede depression during stimulation of the ventrolateral zone. The assortment and pattern of stereotyped movements following injection of the minimal effective dose of amphetamine vary in different ways against the background of these changes. After stimulation of the dorsomedial zones of the nucleus stereotypy is first disorganized and then weakened, whereas caudate activation is associated with strengthening of stereotypy.Department of Pharmacology, Chita Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 6, pp. 518–521, June, 1979.     

LH-RH in picomole concentrations evokes excitation and inhibition of rat arcuate neurones in vitro

A medial sagittal brain slice was developed, which enabled electrophysiological recording from spontaneously active neurones adjacent to the infundibular recess of the rat arcuate nucleus. Luteinizing hormone-releasing hormone (LH-RH) (10 nM-10 pM) significantly altered the frequency of 21 out of 31 units tested, exciting 14 and inhibiting 7 others. The excitatory responses were often not maintained during the exposure to LH-RH but either returned to pre-exposure frequency or displayed an inhibition of discharge. A neural model incorporating recurrent inhibition of LH-RH-excited neurones is proposed to explain these responses, thought to be endogenously evoked by collateral innervation of the arcuate nucleus by medial preoptic neurones projecting to the median eminence.     

Comparison of Changes in Glutamate Levels in the Nucleus Accumbens of the Rat Brain during Food Consumption in Conditions of Blockade of Dopamine D1 and D2 Receptors

The effects of blockade of D₁ and D₂ dopamine receptors in the nucleus accumbens on changes in glutamate levels in the intercellular space of this structure during food consumption were studied in Sprague–Dawley rats by intracerebral microdialysis combined with HPLC. These experiments showed that food consumption was accompanied by decreases in glutamate levels in the intercellular spaces of the nucleus accumbens. Blockade of D₁ dopamine receptors with SCH-23390 (0.01 mM) produced no changes in the dynamics of glutamate release during food consumption. Food consumption in conditions of blockade of D₂ dopamine receptors with raclopride (0.01 mM) induced increases in glutamate levels. These data suggest that glutamate levels during food consumption are controlled by the dopaminergic system of the nucleus accumbens, mediated by D₂ but not D₁ dopamine receptors.