Disturbances of neophobia and taste-aversion learning after bilateral kainate microlesions in the rat pallidum.

These experiments aimed to elucidate feeding-associated behavioral roles of globus pallidus (GP) neurons in gustatory functions: The effects of bilateral microiontophoretic kainate (KA) lesions of the ventromedial pallidal (vmGP) region on neophobia and conditioned taste aversion (CTA) were studied. Lesioned rats displayed strong and persistent neophobia to a mild citric acid solution. Neuron-specific damage to the vmGP also prevented rats from proper acquisition of CTA. Rats that previously showed normal neophobia and successfully learned CTA demonstrated difficulties in CTA retention after GP lesions. KA-lesioned rats, in addition, exhibited deficits in orientation reactions but did not have aphagia, adipsia, or motor disturbances seen after larger pallidal lesions. These findings suggest that neurons of the GP are significant in acquisition, memory storage, and retrieval mechanisms of feeding-associated taste information.

Responses of forebrain neurons to the MAO-B blocker L-deprenyl.

Despite the large amount of neuropharmacological data concerning catecholamine (CA) mechanisms of the mammalian brain, little is known yet about the effects of MAO-inhibitors on single neurons. The present series of experiments aim to elucidate these specific neurochemical attributes of forebrain cells. Single neuron activity was recorded by means of multi-barreled microelectrodes in the caudate nucleus, globus pallidus, and amygdala of both anesthetized rats and anesthetized or alert monkeys during microelectrophoretic application of the MAO-B blocker L-deprenyl (DEPR). CAs (dopamine and noradrenaline), glutamate, GABA, and acetylcholine were also applied. Nearly the half (46%) of all forebrain neurons tested responded, exclusively with inhibition, to DEPR, and the CA-sensitive cells were especially responsive to the MAO-B inhibitor. The time course of DEPR-induced neuronal suppression was short. In some cases, amphetamine (AMPH) and clorgyline (CLOR) were also applied microelectrophoretically. AMPH elicited similar activity changes to those seen after DEPR administrations, whereas CLOR applications were less effective. Our results provide evidence that DEPR can effectively modulate the activity of CA-sensitive neurons in the three different forebrain regions of two different species. On the basis of this data, the possible neurochemical mechanisms of DEPR action are discussed.

Role of forebrain glucose-monitoring neurons in the central control of feeding: II. Complex functional attributes.

Our parallel investigations in the lateral hypothalamic are (LHA), amygdaloid body (AMY) and globus pallidus (GP) provided evidence for the existence of glucose-sensitive (GS) neurons in these forebrain regions. To examine exogenous chemosensory responsiveness of these cells, extracellular single neuron activity was recorded in anesthetized or alert rhesus monkeys and in anesthetized rats during 1) microelectrophoretic administration of chemicals and 2) gustatory and 3) olfactory stimulations. The GS cells in all three forebrain structures were more likely than the glucose-insensitive (GIS) neurons to change in firing rate in response to tastes and smells. The gustatory (and olfactory) GS neurons, compared to the non-gustatory GS or both types of GIS cells, displayed significantly higher sensitivities to catecholamines. Neurons with both "endogenous" and "exogenous" chemosensitivity were found to be topographically organized in the LHA, AMY and GP as well. While receiving further evidence for the substantial morphological and functional overlapping of the brain's glucose-monitoring neural network and the central gustatory representations, on the basis of the present and previous findings, it is suggested that constituents of this complex system accomplish a simultaneous monitoring, integration and control of a broad variety of feeding-associated signals of the internal and external milieux for the biological welfare of the organism.

Role of forebrain glucose-monitoring neurons in the central control of feeding: I. Behavioral properties and neurotransmitter sensitivities.

Extracellular single neuron recording experiments were performed in the lateral hypothalamic area (LHA), amygdaloid body (AMY) and globus pallidus (GP) of anesthetized rats and anesthetized or alert rhesus monkeys during microelectrophoretic administration of different neurochemicals including glucose. Neuron activity in the behaving primate was also investigated during a conditioned bar press alimentary task, as well as during presentation of food and non-food objects. In the LHA, AMY and GP specific glucose-sensitive (GS) neurons were found, as their activity were suppressed by glucose. The proportion of GS neurons was approximately 29%, 11% and 14%, respectively. The GS neurons in the monkey were especially likely to respond to phase of the conditioned alimentary task, and these same neurons appeared to be particularly influenced by sensorimotor and motivational factors. LHA, AMY and GP GS neurons displayed distinct sensitivities to various neurotransmitters applied microelectrophoretically. The present results, along with previous data, indicate that a hirearchically organized network of the brainstem and forebrain glucose-monitoring neurons exit and this system is involved in the regulation of feeding.

Glucose-sensitive neurons of the globus pallidus: I. Neurochemical characteristics.

The lateral hypothalamic area (LHA) and globus pallidus (GP) are basically involved in the regulation of feeding and metabolic processes. In the LHA, glucose-sensitive (GS) neurons were described: their activity was found to be specifically suppressed by electrophoretic application of glucose, and these neurons appeared to be also influenced by various feeding-associated neurochemical signals. The main goal of the present experiments was to examine whether similar GS neurons exist in the GP. In addition, neurochemical attributes of the cells were also tested. In anesthetized rats and anesthetized or awake monkeys, single-neuron activity of the GP was recorded by means of carbon fiber multibarreled microelectrodes and the effects of glucose, glutamate (Gt), GABA, dopamine (DA), noradrenaline (NA) and acetylcholine (Ach) were studied. In both the rat and monkey GP, approximately 12% of the neurons examined responded, with inhibition, to glucose. GP neurons, in a high proportion, were also inhibited by GABA and NA. After application of Gt, DA, or Ach, activity increase or decrease occurred. GS neurons exhibited remarkable sensitivity to these neurochemicals previously identified as neurotransmitters of the complex pallidal, extrapyramidal-limbic neuron loops. The results, along with previous data, indicate that GS cells of the GP, while possessing complex neurochemical characteristics, may belong to a hierarchically organized central glucose-monitoring system essential in the regulation of feeding.

Glucose-sensitive neurons of the globus pallidus: II. Complex functional attributes.

The globus pallidus (GP) is intimately involved in regulation of various aspects of hunger- and thirst-motivated behaviors. Our parallel neurochemical studies demonstrated the existence of GP neurons whose discharge rates are suppressed by glucose applied microelectrophoretically. In the present series of experiments, we aimed to provide complex, feeding-associated functional characterization--similar to that previously accomplished in the case of lateral hypothalamic and amygdaloid chemosensitive neurons--of these glucose-sensitive (GS) and the glucose-insensitive (GIS) pallidal cells. To do so, extracellular single neuron activity of the GP was recorded in anesthetized rats and anesthetized or awake rhesus monkeys by means of carbon fiber, multibarreled glass microelectrodes during: a) microelectrophoretic administration of chemicals, b) gustatory, and c) olfactory stimulations. In alert primates, activity changes were also recorded during presentation of food and nonfood objects as well as during the performance of a conditioned, high fixed-ratio bar-press feeding task. The half of pallidal cells examined showed firing rate changes during phases of the conditioned alimentary task. In both species, about 1/7 of all neurons tested proved to be GS, while the proportion of cells responding to gustatory and olfactory stimulations was 19% and 16%, respectively. Task-related and taste- and smell-responsive units were mainly found among the GS neurons of the pallidum. These data, along with previous findings, indicate that chemosensitive cells of the GP, in an apparent overlap with units of the central gustatory representation, are involved in a hierarchically organized glucose-monitoring neural network, through which pallidal neurons exert their integrative functions in the central feeding control.

Computer analysis of single neuron activity during conditioned feeding task.

A computer controlled complex electrophysiological set-up employing the multibarrel micro-electrophoretic technique is reported in this paper. The laboratory equipped for this technique is used for recording single neuron activity from various sites of the central nervous system of rhesus monkeys during: 1) performing conditioned behavioral tasks, 2) intracerebral microelectrophoretic administration of chemicals, and 3) oral application of gustatory stimuli.