2-deoxyglucose Autoradiography Research Articles

Bilateral Plasticity of Vibrissae SII Representation Induced by Classical Conditioning in Mice

The somatosensory cortex in mice contains primary (SI) and secondary (SII) areas, differing in somatotopic precision, topographic organization, and function. The role of SII in somatosensory processing is still poorly understood. SII is activated bilaterally during attentional tasks and is considered to play a role in tactile memory and sensorimotor integration. We measured the plasticity of SII activation after associative learning based on classical conditioning, in which unilateral stimulation of one row of vibrissae was paired with a tail shock. The training consisted of three daily 10 min sessions, during which 40 pairings were delivered. Cortical activation driven by stimulation of vibrissae was mapped with 2-[(14)C]deoxyglucose (2DG) autoradiography 1 d after the end of conditioning. We reported previously that the conditioning procedure resulted in unilateral enlargement of 2DG-labeled cortical representation of the "trained" row of vibrissae in SI. Here, we measured the width and intensity of the labeled region in SII. We found that both measured parameters in SII increased bilaterally. The increase was observed in cortical layers II/III and IV. Apparently, plasticity in SII is not a simple reflection of changes in SI. It may be attributable to bilateral integrative role of SII, its lesser topographical specificity, and strong involvement in attentional processing.

Local cerebral glucose utilization in rats exposed to an enriched environment: A comparison to impoverishment

Environmental enrichment and environmental impoverishment have been shown to differentially alter brain function. Here, we investigate the effects of enrichment vs. impoverishment on cerebral use of glucose in rodents. Rats were housed from postnatal day 28 to day 58 in either a socially and environmentally enriched environment or an impoverished environment devoid of other rats or environmental stimuli. Locomotor activity was measured at the end of the enrichment/impoverishment period. Following the duration of the exposure to these environments, cerebral metabolic rate of glucose utilization was determined using quantitative 2-[ 14C]deoxyglucose autoradiography in 37 brain regions in the cerebral cortex, forebrain, brain stem and thalamus. There were no differences in locomotor activity between the conditions. The nucleus accumbens core and shell had significantly higher rates of glucose utilization in enriched compared to impoverished animals. These data suggest that environment has a significant effect on brain function which may help to explain the beneficial and protective effects of enrichment against drug abuse and addiction.

Acute challenge with d-fenfluramine decreases regional cerebral glucose utilization in Sham, but not in OBX, rats: An autoradiographic study

The olfactory bulbectomized (OBX) rat is an animal model of depression with neurochemical, neuroendocrinological and behavioral features resembling some human depression. d-Fenfluramine is a 5-HT releasing drug, frequently used in the study of the responsivity of the 5-HT system in subjects with psychiatric disorders, including depression. The aim of the study is to assess the influence of the serotonin-releaser, d-fenfluramine, in the OBX rat model of depression, as measured by the change in the regional cerebral glucose utilization rCGU) following d-fenfluramine injection. Male Sprague–Dawley rats (160–180 g) were used. The rats were divided into OBX and Sham groups. Two weeks following the olfactory bulbectomy or the sham surgery, six rats (randomly assigned) from each group received an i.p. injection of d-fenfluramine with a dose of 5 mg/kg or the same volume of saline. Twenty minutes later, the rCGU rates were measured using 2-[ 14C]deoxyglucose autoradiography. The general linear model statistical analysis has shown that the rCGU in the sham-operated rats treated with d-fenfluramine, compared to the sham-operated rats treated with saline, was lower in 14 (36%) out of 39 examined brain regions. There was no significant difference in the rCGU between the OBX rats treated with d-fenfluramine and OBX rats treated with saline. The results suggest the blunted capacity of the 5-HT system in OBX rats to respond to the challenge by the 5-HT releasing compound, d-fenfluramine. This resembles similar findings in clinical studies on depressed patients.

Subcortical elevation of metabolism in Parkinson's disease — A critical reappraisal in the context of global mean normalization

In a recent issue of NeuroImage, we presented evidence that biased global mean (GM) normalization of brain PET data can generate the appearance of subcortical foci with relative hypermetabolism in patients with Parkinson's disease (PD), and other degenerative disorders. In a commentary to our article, Ma and colleagues presented a study seeking to establish that a pattern of widespread hypermetabolism, known as the Parkinson's disease related pattern (PDRP) is a genuine metabolic feature of PD. In the present paper, we respond to the arguments presented by Ma et al., and we provide a critical reappraisal of the evidence for the existence of the PDRP. To this end, we present new analyses of PET data sets, which demonstrate that very similar patterns of relative subcortical increases are seen in PD, Alzheimer's disease, hepatic encephalopathy, healthy aging, and simulation data. Furthermore, longitudinal studies of PD previously reported relative hypermetabolism in very small anatomical structures such as the subthalamic nucleus. We now demonstrate how focal hypermetabolism attributed to small nuclei can similarly arise as a consequence of GM normalization. Finally, we give a comprehensive summary of the entire deoxyglucose autoradiography literature on acquired parkinsonism in experimental animals. Based on this evidence, we conclude that (1) there is no quantitative evidence for widespread subcortical hypermetabolism in PD, (2) very similar patterns of subcortical hyperactivity are evident in various other brain disorders whenever GM normalization is utilized, and (3) the PDRP is not evident in animal models of PD. In the absence of quantitative evidence for the PDRP, our alternative interpretation of normalization bias seems the more parsimonious explanation for the reports of relative hypermetabolism in PD.

Circling behavior and [14C]2-deoxyglucose mapping in rats: possible implications for autistic repetitive behaviors

Repetitive behaviors (such as circling) are one of the defining features of autism. The substantia nigra (SN) is involved in circling. We used unilateral SN pars reticulata (SNR) infusions of the GABA agonist muscimol to induce circling and deoxyglucose autoradiography mapping in adult and postnatal day (PN) 15 male and female rats to determine its substrates. In adults, muscimol infusions in posterior SNR induced a higher circling rate than in anterior SNR, after which males displayed faster circling than females. In contrast, PN15 female rats circled faster than PN15 male rats. Autoradiograms demonstrated age- and sex-specific alterations of deoxyglucose uptake in the SN pars compacta (SNC) associated with highest circling rates. The data suggest that there is a close relationship of the GABAergic SNR and dopaminergic SNC in the induction of circling; there is a topographic organization of the SNR in terms of circling behavior and associated deoxyglucose uptake, which is dependent on age and sex.

Independent time courses of supraspinal nociceptive activity and spinally mediated behavior during tonic pain

The behavioral response to acute tissue injury is usually characterized by different phases, but the brain mechanisms underlying changes in pain-related behavior over time are still poorly understood. We aimed to analyze time-dependent changes in metabolic activity levels of 49 forebrain structures in the formalin pain model, using the autoradiographic 2-deoxyglucose method in unanesthetized, freely moving rats. We examined rats during the first phase of pain-related reactions (‘early’ groups), or during the third recovery phase, 60 min later, when the supraspinally mediated behavioral responses were reduced (‘late’ group). In the early groups, metabolic rates were bilaterally increased over control values in the periaqueductal gray, zona incerta and in several thalamic nuclei (anteroventral, centrolateral, lateral dorsal, parafascicular, posteromedial, submedius, ventromedial, and ventrobasal complex), as well as in the habenulae and in the parietal, cingulate, antero-dorsal insular, and anterior piriform cortex. A contralateral, somatotopically specific activation was found in the putative hindlimb representation area of the somatosensory cortex. In the late group, noxious-induced activation declined in most structures. However, metabolic rates were higher than controls in the periaqueductal gray and zona incerta and in two other structures not previously active: the prerubral area/field of Forel and the arcuate hypothalamic nucleus. These findings provide a time-dependent functional map of nociceptive and anti-nociceptive forebrain circuits during tonic pain. The parallel decrease in licking behavior and forebrain activity, at times when spinally mediated limb flexion responses were still present, suggests that endogenous antinociceptive systems may differently modulate spinal and supraspinal nociceptive networks following acute tissue injury.

Dose-dependent effects of Delta9-tetrahydrocannabinol on rates of local cerebral glucose utilization in rat.

Recent reports have demonstrated that Delta(9)-tetrahydrocannabinol (Delta(9)-THC) stimulates locomotor activity at low doses (<2.5 mg/kg), while higher doses (>2.5 mg/kg) produce decreases in spontaneous activity. Using quantitative 2-[(14)C]deoxyglucose (2-DG) autoradiography, we systematically studied the effects of acute Delta(9)-THC on rates of local cerebral glucose utilization. The first series of experiments was designed to determine if Delta(9)-THC-mediated changes in cerebral metabolism followed a clear dose-response relationship. Adult male Sprague-Dawley rats were treated with either vehicle or Delta(9)-THC (0.25-2.5 mg/kg) and the 2-DG procedure was initiated 15 min following exposure. Administration of 2.5 mg/kg Delta(9)-THC produced significant decreases in cerebral metabolism in most brain regions studied. In contrast, administration of 0.25 mg/kg Delta(9)-THC produced no significant alterations in any brain region studied, while 1.0 mg/kg of Delta(9)-THC produced a restricted pattern of metabolic decreases. Significant decreases in metabolism following 1.0 mg/kg were concentrated in structures subserving limbic and sensory functions. In a second series of experiments, the effects of pretreatment with the cannabinoid receptor antagonist SR141716A (1.0 mg/kg) on Delta(9)-THC-induced changes in functional activity were measured. Pretreatment with SR141716A attenuated the majority of functional changes produced by Delta(9)-THC, suggesting that these effects are primarily mediated by central cannabinoid receptors. Moreover, these findings indicate that the effects of Delta(9)-THC on cerebral metabolism are dose-dependent and that there are regional differences in the metabolic response to acute cannabinoid exposure.

Effects of lesions of the medial preoptic nucleus on the testosterone-induced metabolic changes in specific brain areas in male quail

The effects of bilateral lesions of the medial preoptic nucleus in association with testosterone on the metabolic activity in discrete brain regions was studied quantitatively by the in vivo autoradiographic 2-deoxyglucose method. Adult male quail were castrated and then left without hormone replacement therapy or treated with testosterone or treated with testosterone and submitted to a bilateral lesion of the medial preoptic nucleus, a brain region that plays a key role in the activation of male copulatory behavior by testosterone. Treatment for about 10 days with testosterone activated the expression of the full range of male sexual behaviors and these behaviors were completely suppressed by the medial preoptic nucleus lesions. Mapping of 2-deoxyglucose uptake revealed both increases and decreases of metabolic activity in discrete brain regions associated with the systemic treatment with testosterone as well as with the lesion of the medial preoptic nucleus. Testosterone affected the oxidative metabolism in brain areas that are known to contain sex steroid receptors (such as the nucleus taeniae and the paraventricular and ventromedial nuclei of the hypothalamus) but also in nuclei that are believed to be devoid of such receptors. Effects of testosterone in these nuclei may be indirect or reflect changes in terminals of axons originating in steroid-sensitive areas. Bilateral medial preoptic nucleus lesions affected 2-deoxyglucose uptake in a variety of brain regions. Some of these regions are known to be mono-synaptically connected to the medial preoptic nucleus. Metabolic depression in these areas may reflect retrograde changes in the neurons projecting to the damaged field.The metabolic changes identified in the present study confirm the prominent role of the preoptic area in the control of sexual behavior, show that changes in the physiology of the visual system represent one of the ways through which testosterone influences the occurrence of this behavior and demonstrate that the medial preoptic nucleus has marked effects on the metabolic activity in a variety of limbic and telencephalic structures. This study also indicates that the medial preoptic nucleus affects the activity of the area ventralis of Tsai, a dopaminergic area known to send projections to a variety of hypothalamic, thalamic and mesencephalic nuclei that are implicated in the control of male sexual behavior. These data therefore support the notion that the control of the dopaminergic activity in the area ventralis of Tsai by the medial preoptic nucleus represents one of the ways through which the medial preoptic area regulates male reproductive behavior.

Metabolic activity in optic tectum during regeneration of retina in adult goldfish.

Retinal and visual function returns following retinal destruction by ouabain in adult goldfish (Carassius auratus). Although the precise cellular mechanisms are unclear, the ability to regenerate CNS neurons and connections that subsequently sustain visual behavior is remarkable, especially for an adult vertebrate. In this paper, we ask whether visual stimulation via new retinal cells can activate existing cells in the optic tectum, which normally receives the largest retinal projection in this species. The right eyes of adult goldfish were injected with ouabain. After 1-18 weeks the conscious, freely moving fish were exposed to spatially and temporally varying visual stimuli and the resulting tectal metabolic activity was determined with the autoradiographic deoxyglucose method. In normal controls without lesions, visual stimulation produced equally strong metabolic activity in both tectal hemispheres, peaking in the layer where most retinotectal projections terminate (N = 6). One week after ouabain injection, metabolic activity in the contralateral, deprived tectum was dramatically reduced (N = 5), closely resembling the effect of unilateral ocular enucleation (N = 5). However, 9-18 weeks after ouabain injection, metabolic activity in the deprived tectum recovered to a level that was statistically indistinguishable from normal controls (N = 6). These findings suggest that, after a comprehensive cytotoxic lesion of the retina, regenerated ganglion cells not only establish new connections with the preexisting optic tectum, but also effectively transmit visual information they receive from newly generated photoreceptors to the "old" tectum.

Effects of xenon on cerebral blood flow and cerebral glucose utilization in rats.

The effects of xenon inhalation on mean and local cerebral blood flow (CBF) and mean and local cerebral glucose utilization (CGU) were investigated using iodo-[14C]antipyrine and [14C]deoxyglucose autoradiography. Rats were randomly assigned to the following groups: conscious controls (n = 12); 30% (n = 12) or 70% xenon (n = 12) for 45 min for the measurement of local CBF and CGU; or 70% xenon for 2 min (n = 6) or 5 min (n = 6) for the measurement of local CBF only. Compared with conscious controls, steady state inhalation of 30 or 70% xenon did not result in changes of either local or mean CBF. However, mean CBF increased by 48 and 37% after 2 and 5 min of 70% xenon short inhalation, which was entirely caused by an increased local CBF in cortical brain regions. Mean CGU determined during steady state 30 or 70% xenon inhalation remained unchanged, although local CGU decreased in 7 (30% xenon) and 18 (70% xenon) of the 40 examined brain regions. The correlation between CBF and CGU in 40 local brain structures was maintained during steady state inhalation of both 30 and 70% xenon inhalation, although at an increased slope at 70% xenon. Effects of 70% xenon inhalation on CBF in rats are time-dependent. During steady state xenon inhalation (45 min), mean values of CBF and CGU do not differ from control values, and the relation of regional CBF to CGU is maintained, although reset at a higher level.

Performance of appetitive or consummatory components of male sexual behavior is mediated by different brain areas: a 2-deoxyglucose autoradiographic study

The in vivo autoradiographic deoxyglucose method was used to identify the functional brain circuits that are involved in the performance of appetitive and consummatory components of male sexual behavior in Japanese quail ( Coturnix japonica). Two groups of castrated, testosterone-treated male quail were trained during 12 sessions to associate the view of a female behind a window with the opportunity to interact freely and to copulate with her. They developed, as a consequence, a social proximity response (staying close and looking through the window providing a view of the female) that has been used in previous experiments to measure appetitive sexual behavior. A third control group (also castrated and treated with testosterone) was allowed to view the female but not to copulate with her and therefore did not develop this proximity response. 2- 14C-deoxyglucose was then injected i.p. to these birds and they were allowed to either copulate freely with a female (consummatory sexual behavior group) or express the social proximity response (appetitive sexual behavior group). The control group was provided a view of the female but these birds, although they were exposed to the same stimuli as birds in the appetitive group, did not express the social proximity response because they had never learned the association with the opportunity to copulate. Birds were killed 45 min after the deoxyglucose injection and their brains were processed for autoradiography. Densitometric analyses of the autoradiograms revealed that the expression of appetitive or consummatory aspects of male sexual behavior was associated with significant increases by comparison with the control group in the deoxyglucose incorporation in the nucleus mesencephalicus lateralis, pars dorsalis and in the nucleus leminsci lateralis. In addition, an increase in the deoxyglucose incorporation was specifically observed in the paleostriatum primitivum, rostral preoptic area, nucleus intercollicularis, nucleus interpeduncularis and third nerve but a decrease was observed in the dorsomedial part of the hippocampus and in the nucleus nervi oculomotori in birds of the consummatory sexual behavior group by comparison with controls. By contrast, in the appetitive sexual behavior group, significant increases in deoxyglucose incorporation were observed in two telencephalic areas, the intermediate hyperstriatum ventrale and neostriatum caudolaterale by comparison with the controls, but decreases were detected in the stratum griseum et fibrosum superficiale of optic tectum by comparison with the consummatory behavior group. These studies demonstrate that the performance of appetitive or consummatory components of male sexual behavior affects in a specific manner the deoxyglucose uptake and accumulation in specific regions of the quail brain. Changes in metabolic activity were observed in steroid-sensitive areas, in auditory, visual and vocal brain regions, and in brain nuclei related to motor behavior but also in association telencephalic and limbic structures. These changes in oxidative metabolism overlap to some extent with metabolic changes as revealed by immunocytochemistry for the immediate early gene products Fos and Zenk, but many specific reactions are also detected indicating that these techniques are not necessarily redundant and, together, they can provide a more complete picture of the brain circuits that are implicated in the control and performance of complex behaviors.

Metabolic activity changes in the rat spinal cord during adjuvant monoarthritis

The development of chronic pain is associated with activity-dependent plastic changes in neuronal structures in the peripheral and central nervous system. In order to investigate the time-dependent processing of afferent noxious stimuli in the spinal cord we employed the quantitative autoradiographic 2-deoxyglucose technique in a model of chronic monoarthritic pain in the rat. Spinal metabolic activity was determined at various time-points (two, four and 14 days) after the injection of complete Freund's adjuvant into the left tibiotarsal joint. In addition, the effect of acute noxious mechanical stimulation of the arthritic joint was investigated at 14 days of monoarthritis. Local glucose utilization was determined in lumbar segments L 2–L 5, ipsi- and contralateral to the inflamed hindpaw, and compared with saline-injected controls. In general, monoarthritic animals had bilaterally increased metabolic activity in all laminae of the spinal cord. Detailing the time-course showed that in rats with two days of monoarthritis metabolic activity was significantly increased to a similar extent on both sides of all spinal laminae. In contrast, at four days, glucose utilization in deep laminae of the dorsal horn (laminae V–VI), the central gray area (laminae X) and the ventral horn (laminae VII–IX) tended to return to control levels. At 14 days of monoarthritis, however, metabolic activity showed a further increase in all laminae of the spinal cord. This increase was more pronounced on the side ipsilateral to inflammation, reaching 65% above corresponding control levels in laminae V, VI. Animals with 14 days of monoarthritis which were subjected to mechanical noxious stimulation of the arthritic joint displayed clear behavioral signs of acute pain. Although in this group metabolic activity was above control levels, it was lower than in animals with 14 days of monoarthritis that were not additionally stimulated. The data show not only a general increase of spinal cord metabolic activity during the time-course of the development of a chronic pain state, but also show a region-specific non-linear time profile. This may reflect the complexity of transducing and suppressive transmitter systems involved in the central processing of ongoing pain.

Partial denervation of the whiskerpad in adult mice: altered patterns of metabolic activity in barrel cortex

One hundred days after unilateral C-row nerve transection in the adult mouse whiskerpad, the caudal follicles of row C are reinnervated with approximately 80 % of the original number of axons [Corthésy, M.-E., Bronchti, G. & Welker, E. (1999) Eur. J. Neurosci. , 11, 2835-2846]. To what extent is this reinnervation functional, and how does it interact with the enlargement of the functional representation of neighbouring rows subsequent to the denervation? Using the autoradiographic deoxyglucose method, we studied the whisker representation at the level of the barrel cortex 100 days post lesionem. We stimulated whiskers belonging to the denervated row C, the neighbouring rows B and D, or to all five rows A-E. The deoxyglucose uptake was measured in tangential sections through layer IV. The results indicate that, 100 days post lesionem, whiskers of row C reactivate their cortical barrels. However, (i) the magnitude of this cortical response was reduced; (ii) row C barrels were equivalently activated by the stimulation of the neighbouring rows; and (iii) when all whiskers were stimulated, we observed a significantly reduced deoxyglucose uptake over the representation of nonlesioned whiskers of rows D and E. Therefore, 100 days after the peripheral nerve lesion the reinnervation of the whiskerpad had not restored a normal pattern of activation at the level of the barrel cortex. We propose that this is due to a modified interaction between the representations of the various rows of follicles at the cortical level that does not return to normal.

Medial Forebrain Bundle Lesions Fail to Structurally and Functionally Disconnect the Ventral Tegmental Area from Many Ipsilateral Forebrain Nuclei: Implications for the Neural Substrate of Brain Stimulation Reward

Lesions in the medial forebrain bundle rostral to a stimulating electrode have variable effects on the rewarding efficacy of self-stimulation. We attempted to account for this variability by measuring the anatomical and functional effects of electrolytic lesions at the level of the lateral hypothalamus (LH) and by correlating these effects to postlesion changes in threshold pulse frequency (pps) for self-stimulation in the ventral tegmental area (VTA). We implanted True Blue in the VTA and compared cell labeling patterns in forebrain regions of intact and lesioned animals. We also compared stimulation-induced regional [14C]deoxyglucose (DG) accumulation patterns in the forebrains of intact and lesioned animals. As expected, postlesion threshold shifts varied: threshold pps remained the same or decreased in eight animals, increased by small but significant amounts in three rats, and increased substantially in six subjects. Unexpectedly, LH lesions did not anatomically or functionally disconnect all forebrain nuclei from the VTA. Most septal and preoptic regions contained equivalent levels of True Blue label in intact and lesioned animals. In both intact and lesioned groups, VTA stimulation increased metabolic activity in the fundus of the striatum (FS), the nucleus of the diagonal band, and the medial preoptic area. On the other hand, True Blue labeling demonstrated anatomical disconnection of the accumbens, FS, substantia innominata/magnocellular preoptic nucleus (SI/MA), and bed nucleus of the stria terminalis. [14C]DG autoradiography indicated functional disconnection of the lateral preoptic area and SI/MA. Correlations between patterns of True Blue labeling or [14C]deoxyglucose accumulation and postlesion shifts in threshold pulse frequency were weak and generally negative. These direct measures of connectivity concord with the behavioral measures in suggesting a diffuse net-like connection between forebrain nuclei and the VTA.

Excitability changes and glucose metabolism in experimentally induced focal cortical dysplasias.

Malformations of cortical development are increasingly recognized in association with severe epileptic syndromes, neuropsychological disorders and mental retardation. Several clinical and experimental studies suggest that functional consequences of cortical dysplasias are not restricted to the area of the dysplastic lesion but also involve remote brain regions. In the present study cortical malformations were induced in newborn rats at day of birth by intracerebral injection of the glutamatergic agonist ibotenate. The resulting cytoarchitectonic lesion associates neuronal depopulation of deep cortical layers, ectopic neurons in superficial layers and sulcus formation, mimicking human polymicrogyria and migration disorders. Electrophysiological recordings of evoked field potentials in slice preparations of adult animals reveal hyperexcitability in widespread cortical regions surrounding the dysplasia. Low-intensity stimulation induced epileptiform activity consisting of long-lasting, multiphasic and N-methyl-D-aspartate-dependent field responses. They appeared with high variability as all-or-none events. These widespread changes in excitability were not observed in sham-operated animals with small superficial ectopias but intact deep cortical layers, indicating that focal loss of these layers induces extended alterations in cortical connectivity and imbalance of excitation and inhibition. Restricted zones of increased excitability were also found in the forelimb and hindlimb representation cortex in sham-operated and control animals, demonstrating that this activity has to be considered as an intrinsic property of specific cortical areas. Deoxyglucose autoradiography showed that the widespread hyperexcitability in ibotenate-injected animals was not accompanied by alterations in glucose metabolism, although in the area of structural abnormality a typical metabolic pattern was found, revealing an increased glucose uptake in layer I. Hypometabolism as described for many types of human dysplastic lesions was not observed. This difference between the experimental and clinical data may be due to the absence of behavioral seizures in this model. However, it can be hypothesized that in patients with developmental malformations, additional pathogenic factors contribute to the manifestation of seizure disorders.

Change in cerebral glucose metabolism during limbic seizures elicited from lateral septal nucleus.

The roles of the amygdala and hippocampus have been extensively studied in limbic seizures. Although the septal nuclei have a close connection to the hippocampus and affect emotional behavior, the effect on limbic seizures is still unclear. We have reported that characteristic sham-rage seizures were observed in cats, by administering a local injection of kainic acid (KA) into the lateral septal nucleus (LSN). This study investigated the electrophysiological features of KA-induced septal seizures in rats and analyzed the process in relation to the cerebral glucose metabolism using [14C]deoxyglucose autoradiography. On EEG, epileptic discharge eliciting from the LSN rapidly propagated to the hippocampus and the amygdala. Behavioral change was similar to that in limbic seizures induced by intraamygdaloid KA. Sham-rage seizure was not observed in rats. However, the local cerebral glucose metabolism during the seizures increased not only in the limbic structures including the LSN but also in the hypothalamus and periaqueductal grey matter of the midbrain. The findings were distinctive of septal seizures as compared with amygdaloid seizures. The results suggested that sham-rage seizures in cats might be caused by a secondary epileptogenic excitation in the hypothalamus or periaqueductal grey matter of the midbrain. The septal nuclei may play an important role in emotional behavior associated with limbic seizures even if there is a species difference in its function.

Brain hypometabolism in a model of chronic focal epilepsy in rat neocortex.

Metabolic mapping of the human brain has become a widely used method for identifying and localizing epileptic foci. A reduction of glucose consumption usually is found interictally in the area of the focus. By contrast, animal models of acute epilepsy show a hypermetabolism in the epileptic focus. Here we investigated how metabolism is altered in an animal model of chronic epilepsy caused by focal injection of tetanus toxin into rat neocortex. A total of 27 male Wistar rats were anesthetized and injected into the motor or sensory cortex either with dissolved tetanus toxin or with the solvent only. Animals recovered for 7, 14, or 30 days and then were anesthetized again for quantitative 14C-deoxyglucose autoradiography. Data were analyzed with an imaging program, and regional cerebral glucose metabolism (rCMRGlc) was determined. Injection of tetanus toxin into the motor cortex caused a focal hypometabolism which was confined to the cytoarchitectonic boundaries of the injected area, whereas sensory cortex injection caused a more widespread hypometabolism in all sensory cortical and connected, areas. None of the animals displayed focal hypermetabolism and we observed no significant time-dependent alteration of brain metabolism. Tetanus toxin injection into the cortex of the rat induces chronic epileptic activity accompanied by a focal hypometabolism. The data suggest that the spread of the metabolic alterations depends on the connectivity of the injected cortical area.

Induction of FOS and JUN proteins during focal epilepsy: congruences with and differences to [14C]deoxyglucose metabolism.

fos and jun belong to multigene families coding for transcription factors. These cellular immediate-early genes (IEGs) are thought to be involved in coupling neuronal excitation to changes of target gene expression. Immunocytochemistry with specific antisera was used to assess regional levels of five IEG-encoded proteins (c-FOS, FOS B, c-JUN, JUN B and JUN D) in a rat model of penicillin-induced focal epilepsy. To assess whether brain regions with post-ictal de novo transcription factor synthesis correspond to those areas with increased glucose metabolism, IEG expression patterns were compared with [14C]deoxyglucose autoradiography performed in a subset of animals. The results demonstrated marked induction of c-FOS, FOS B, c-JUN and JUN B but not JUN D in the cortical epileptic focus. Thereby, individual IEG-encoded proteins exhibited differential temporal and spatial expression patterns. Within the epileptic focus, IEG expression correlated with increased glucose metabolism. In contrast, IEG induction was not observed in brain areas distant from the epileptic focus that also demonstrated increased glucose metabolism, such as homotopic contralateral motor cortex and ipsilateral thalamic nuclei. These findings indicate that in focal epilepsy changes of the genetic programme are restricted to neurons of the epileptic focus. In contrast, the increased [14C]deoxyglucose metabolism in contralateral motor cortex and ipsilateral thalamus seems to indicate functional changes.

The mechanism of the attenuation of c-fos response to the acute stress in the PVH in repeatedly stressed rats

The effects of bilateral lesions of the medial preoptic nucleus in association with testosterone on the metabolic activity in discrete brain regions was studied quantitatively by the in vivo autoradiographic 2-deoxyglucose method. Adult male quail were castrated and then left without hormone replacement therapy or treated with testosterone or treated with testosterone and submitted to a bilateral lesion of the medial preoptic nucleus, a brain region that plays a key role in the activation of male copulatory behavior by testosterone. Treatment for about 10 days with testosterone activated the expression of the full range of male sexual behaviors and these behaviors were completely suppressed by the medial preoptic nucleus lesions. Mapping of 2-deoxyglucose uptake revealed both increases and decreases of metabolic activity in discrete brain regions associated with the systemic treatment with testosterone as well as with the lesion of the medial preoptic nucleus. Testosterone affected the oxidative metabolism in brain areas that are known to contain sex steroid receptors (such as the nucleus taeniae and the paraventricular and ventromedial nuclei of the hypothalamus) but also in nuclei that are believed to be devoid of such receptors. Effects of testosterone in these nuclei may be indirect or reflect changes in terminals of axons originating in steroid-sensitive areas. Bilateral medial preoptic nucleus lesions affected 2-deoxyglucose uptake in a variety of brain regions. Some of these regions are known to be mono-synaptically connected to the medial preoptic nucleus. Metabolic depression in these areas may reflect retrograde changes in the neurons projecting to the damaged field.The metabolic changes identified in the present study confirm the prominent role of the preoptic area in the control of sexual behavior, show that changes in the physiology of the visual system represent one of the ways through which testosterone influences the occurrence of this behavior and demonstrate that the medial preoptic nucleus has marked effects on the metabolic activity in a variety of limbic and telencephalic structures. This study also indicates that the medial preoptic nucleus affects the activity of the area ventralis of Tsai, a dopaminergic area known to send projections to a variety of hypothalamic, thalamic and mesencephalic nuclei that are implicated in the control of male sexual behavior. These data therefore support the notion that the control of the dopaminergic activity in the area ventralis of Tsai by the medial preoptic nucleus represents one of the ways through which the medial preoptic area regulates male reproductive behavior.

712 The mechanism of the attenuation of c-fos response to the acute stress in the PVH in repeatedly stressed rats

The effects of bilateral lesions of the medial preoptic nucleus in association with testosterone on the metabolic activity in discrete brain regions was studied quantitatively by the in vivo autoradiographic 2-deoxyglucose method. Adult male quail were castrated and then left without hormone replacement therapy or treated with testosterone or treated with testosterone and submitted to a bilateral lesion of the medial preoptic nucleus, a brain region that plays a key role in the activation of male copulatory behavior by testosterone. Treatment for about 10 days with testosterone activated the expression of the full range of male sexual behaviors and these behaviors were completely suppressed by the medial preoptic nucleus lesions. Mapping of 2-deoxyglucose uptake revealed both increases and decreases of metabolic activity in discrete brain regions associated with the systemic treatment with testosterone as well as with the lesion of the medial preoptic nucleus. Testosterone affected the oxidative metabolism in brain areas that are known to contain sex steroid receptors (such as the nucleus taeniae and the paraventricular and ventromedial nuclei of the hypothalamus) but also in nuclei that are believed to be devoid of such receptors. Effects of testosterone in these nuclei may be indirect or reflect changes in terminals of axons originating in steroid-sensitive areas. Bilateral medial preoptic nucleus lesions affected 2-deoxyglucose uptake in a variety of brain regions. Some of these regions are known to be mono-synaptically connected to the medial preoptic nucleus. Metabolic depression in these areas may reflect retrograde changes in the neurons projecting to the damaged field.The metabolic changes identified in the present study confirm the prominent role of the preoptic area in the control of sexual behavior, show that changes in the physiology of the visual system represent one of the ways through which testosterone influences the occurrence of this behavior and demonstrate that the medial preoptic nucleus has marked effects on the metabolic activity in a variety of limbic and telencephalic structures. This study also indicates that the medial preoptic nucleus affects the activity of the area ventralis of Tsai, a dopaminergic area known to send projections to a variety of hypothalamic, thalamic and mesencephalic nuclei that are implicated in the control of male sexual behavior. These data therefore support the notion that the control of the dopaminergic activity in the area ventralis of Tsai by the medial preoptic nucleus represents one of the ways through which the medial preoptic area regulates male reproductive behavior.