Separation of electrophysiologically distinct neuronal populations in the rat hippocampus for neuropharmacological testing under in vivo conditions.

Microiontophoresis combined with extracellular spike recording is an excellent method for investigating local neuropharmacological effects under in vivo conditions. However, its application has recently become relatively rare in neuroscience research. Now, we aimed to revisit microiontophoresis and demonstrate that it provides valuable data about the pharmacophysiology of neurons and local neuronal networks, in vivo. Extracellular recordings were performed through the central recording channel of multibarrel carbon-fiber microelectrodes in the CA1 pyramidal layer of the hippocampus of anesthetized rats, while N-methyl-D-aspartate (NMDA) was locally administrated by means of microiontophoresis through the surrounding micropipettes of the microelectrode. Various separation procedures were used to distinguish putative pyramidal cells and interneurons. Quality of separation was verified by electrophysiological parameters. After the delivery of NMDA in the vicinity of the examined neurons, firing rate of putative pyramidal cells was increased with a significantly higher grade then that of putative interneurons. The present results in line with previous data indicate that pyramidal cells are more responsive to pharmacological manipulation through NMDA receptors, also confirming the reliability of the separation of different types of neurons in in vivo microiontophoretic experiments.

Automatic detection of trustworthiness of the face: a visual mismatch negativity study.

Recognizing intentions of strangers from facial cues is crucial in everyday social interactions. Recent studies demonstrated enhanced event-related potential (ERP) responses to untrustworthy compared to trustworthy faces. The aim of the present study was to investigate the electrophysiological correlates of automatic processing of trustworthiness cues in a visual oddball paradigm in two consecutive experimental blocks. In one block, frequent trustworthy (p = 0.9) and rare untrustworthy face stimuli (p = 0.1) were briefly presented on a computer screen with each stimulus consisting of four peripherally positioned faces. In the other block stimuli were presented with reversed probabilities enabling the comparison of ERPs evoked by physically identical deviant and standard stimuli. To avoid attentional effects participants engaged in a central detection task. Analyses of deviant minus standard difference waveforms revealed that deviant untrustworthy but not trustworthy faces elicited the visual mismatch negativity (vMMN) component. The present results indicate that adaptation occurred to repeated unattended trustworthy (but not untrustworthy) faces, i.e., an automatic expectation was elicited towards trustworthiness signals, which was violated by deviant untrustworthy faces. As an evolutionary adaptive mechanism, the observed fast detection of trustworthiness-related social facial cues may serve as the basis of conscious recognition of reliable partners.

Novelty response of rats determines the effect of prefrontal alpha-2 adrenoceptor modulation on anxiety.

In this study we provide evidence that animals of the same population, although identical in age and sex, have individual reactions to the prefrontal modulation of adrenoceptors. We have examined the dose-dependent action of α(2)-adrenoceptor agents on the anxiety of rats with different response to novelty in the elevated plus maze (EPM) apparatus. Rats were divided into high (HR) and low responder (LR) groups based on their locomotor activity in a novel open field environment. HR rats also showed increased locomotion and low anxiety in the EPM. Prefrontal injection of α(2)-receptor antagonist yohimbine, BRL44408 or imiloxan caused anxiety only in HR rats. The α(2A/D)-receptor agonist guanfacine increased anxiety levels of both groups. However, the effective dose was lower in HR rats. The present results propose different prefrontal adrenoceptor sensitivity of rats showing distinct baseline activity levels.

Effects of twenty-minute 3G mobile phone irradiation on event related potential components and early gamma synchronization in auditory oddball paradigm.

We investigated the potential effects of 20 min irradiation from a new generation Universal Mobile Telecommunication System (UMTS) 3G mobile phone on human event related potentials (ERPs) in an auditory oddball paradigm. In a double-blind task design, subjects were exposed to either genuine or sham irradiation in two separate sessions. Before and after irradiation subjects were presented with a random series of 50 ms tone burst (frequent standards: 1 kHz, P=0.8, rare deviants: 1.5 kHz, P=0.2) at a mean repetition rate of 1500 ms while electroencephalogram (EEG) was recorded. The subjects' task was to silently count the appearance of targets. The amplitude and latency of the N100, N200, P200 and P300 components for targets and standards were analyzed in 29 subjects. We found no significant effects of electromagnetic field (EMF) irradiation on the amplitude and latency of the above ERP components. In order to study possible effects of EMF on attentional processes, we applied a wavelet-based time-frequency method to analyze the early gamma component of brain responses to auditory stimuli. We found that the early evoked gamma activity was insensitive to UMTS RF exposition. Our results support the notion, that a single 20 min irradiation from new generation 3G mobile phones does not induce measurable changes in latency or amplitude of ERP components or in oscillatory gamma-band activity in an auditory oddball paradigm.

Alterations of conditioned taste aversion after microiontophoretically applied neurotoxins in the medial prefrontal cortex of the rat.

The prefrontal cortex (PFC) has been reported to be essential in neural control of feeding. In the present study, we aimed to provide a complex characterization of behavioral consequences of PFC microlesions in CFY rats. Kainic acid (KA) was microiontophoretically applied into the mediodorsal division of PFC to damage intrinsic neurons, whereas in another group of rats, 6-hydroxydopamine (6-OHDA) was microiontophoretized into the same region to destroy catecholaminergic (CA) projection fiber terminals. Body weights, food and fluid intake of both lesioned and (sham-operated or intact) control animals were daily measured. Effects of intracellular dehydration and water deprivation were also studied. Open field activity, stereotyped behaviors, and orientation towards visual and somesthetic stimuli were pre- and postoperatively tested. To examine hypothesized consequences of mPFC microlesions on central taste information processing, the acquisition and retention of saccharine conditioned taste aversion (CTA) were studied. No major changes were recorded in body weights, food and water consumption. Dehydration or deprivation similarly increased water intake in all animals. Scores of open field activity and stereotyped behaviors in the 6-OHDA group were significantly higher than those of the other groups. As the main findings of the present studies, both KA and 6-OHDA lesioned rats displayed significant deficits in CTA acquisition and retention tests. These results suggest that the medial PFC has a substantial role in both the formation and the retrieval of CTA. Furthermore, the present findings also indicate the general significance of prefrontal CA mechanisms in the organization of goal-directed, adaptive behaviors.

Bombesin injection into the central amygdala influences feeding behavior in the rat.

The present study was performed to determine whether low doses (10 or 40 ng) of bombesin microinjected into the amygdala could modify solid food intake. Forty ng of bombesin in 24 h deprived rats caused transient inhibition of food intake. This inhibitory effect was eliminated by prior bombesin antagonist treatment. A series of quantitative behavioral tests indicated that low doses of bombesin application specifically reduced food intake without altering the behavioral pattern or influencing the body temperature. The present results suggest, that bombesin-like peptides may act as a satiety signal in the central part of the amygdala.

Responses to the sensory properties of fat of neurons in the primate orbitofrontal cortex.

The primate orbitofrontal cortex is a site of convergence of information from primary taste, olfactory, and somatosensory cortical areas. We describe the responses of a population of single neurons in the orbitofrontal cortex that responds to fat in the mouth. The neurons respond, when fatty foods are being eaten, to pure fat such as glyceryl trioleate and also to substances with a similar texture but different chemical composition such as paraffin oil (hydrocarbon) and silicone oil [Si(CH3)2O)n]. This is evidence that the neurons respond to the oral texture of fat, sensed by the somatosensory system. Some of the population of neurons respond unimodally to the texture of fat. Other single neurons show convergence of taste inputs, and others of olfactory inputs, onto single neurons that respond to fat. For example, neurons were found that responded to the mouth feel of fat and the taste of monosodium glutamate (both found in milk), or to the mouth feel of fat and to odor. Feeding to satiety reduces the responses of these neurons to the fatty food eaten, but the neurons still respond to some other foods that have not been fed to satiety. Thus sensory-specific satiety for fat is represented in the responses of single neurons in the primate orbitofrontal cortex. Fat is an important constituent of food that affects its palatability and nutritional effects. The findings described provide evidence that the reward value (or pleasantness) of the mouth feel of fat is represented in the primate orbitofrontal cortex and that the representation is relevant to appetite.

The neurophysiology of taste and olfaction in primates, and umami flavor.

To investigate the neural encoding of glutamate (umami) taste in the primate, recordings were made from taste responsive neurons in the cortical taste areas in macaques. Most of the neurons were in the orbitofrontal cortex (secondary) taste area. First, it was shown that there is a representation of the taste of glutamate which is separate from the representation of the other prototypical tastants sweet (glucose), salt (NaCl), bitter (quinine) and sour (HCl). Second, it was shown that single neurons that had their best responses to sodium glutamate also had good responses to glutamic acid. Third, it was shown that the responses of these neurons to the nucleotide umami tastant inosine 5'-monophosphate were more correlated with their responses to monosodium glutamate than to any prototypical tastant. Fourth, concentration response curves showed that concentrations of monosodium glutamate as low as 0.001 M were just above threshold for some of these neurons. Fifth, some neurons in the orbitofrontal region, which responded to monosodium glutamate and other food tastes, decreased their responses after feeding with monosodium glutamate to behavioral satiety, revealing a mechanism of satiety. In some cases this reduction was sensory-specific. Sixth, it was shown in psychophysical experiments in humans that the flavor of umami is strongest with a combination of corresponding taste and olfactory stimuli (e.g., monosodium glutamate and garlic odor). The hypothesis is proposed that part of the way in which glutamate works as a flavor enhancer is by acting in combination with corresponding food odors. The appropriate associations between the odor and the glutamate taste may be learned at least in part by olfactory to taste association learning in the primate orbitofrontal cortex.

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.

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.

Predicting pure tone thresholds in normal and hearing-impaired ears with distortion product emission and age.

Distortion product emission (DPE) growth functions, demographic data, and pure tone thresholds were recorded in 229 normal-hearing and hearing-impaired ears. Half of the data set (115 ears) was used by a discriminant analysis routine to classify DPE and demographic features into either a normal pure tone threshold (PTT) group or an impaired PTT group (PTT greater than 30 dB SPL) at six frequencies in the audiometric range. The six discriminant functions developed from this classification process were then used to predict pure tone threshold group membership in the remaining 114-ear data set. Frequency-specific prediction accuracy varied from 71% (correct classification of hearing impairment at 1025 Hz) to 92% (correct classification of normal hearing at 2050 Hz). Of the 45 DPE and demographic variables evaluated, the DPE amplitude associated with an f2 of moderate level (50 dB SPL) and a frequency corresponding to pure tone threshold was generally most predictive. DPE level was found to be weakly correlated with subject age and perhaps for this reason age was frequently included in discriminant functions. For our data, discriminant functions with one variable, two variables, or 5-10 variables showed no differences in predictive performance. This research suggests that DPE measures can reliably categorize pure tone thresholds as normal or impaired in large populations with varied cochlear hearing status.