Biomedical subjects

F Gonzalez-Lima

Publications and source records attributed to F Gonzalez-Lima.

At least 37 records · Page 2Linked to original sources

PubMed2002

Water maze training in aged rats: effects on brain metabolic capacity and behavior.

The effects of Morris water maze training on brain metabolism and behavior were compared between aged (20-22 months) and young (2-4 months) Fischer 344 male rats. Each group had yoked controls, which swam the same amount of time as the trained rats but without the platform. This was followed after 9 days by quantitative histochemical mapping of brain cytochrome oxidase, the terminal enzyme for cellular respiration. The aged rats spent a significantly lower percent of time in the correct quadrant and had a longer latency to escape to the hidden platform, relative to the young rats. Metabolic differences between trained aged and young rats were found in regions related to escape under stress: perirhinal cortex, basolateral amygdala and lateral habenula; and vestibular nuclei that guide orientation in three-dimensional space. These differences were not found in the yoked swimming rats. The results suggest that, at the time point investigated, water maze training in aged Fischer 344 rats produces altered oxidative energy metabolism in task-relevant limbic and vestibular regions.

Aging↗

PubMed2002

Repeated interactions with females elevate metabolic capacity in the limbic system of male rats.

The effect of heterosexual social experience on brain metabolic capacity was investigated by measuring the activity of cytochrome oxidase, a rate-limiting enzyme in oxidative metabolism. Male Sprague-Dawley rats were kept naïve or allowed to copulate with receptive females three (3 F males) or 16 times (16 F males). Throughout the vomeronasal system and other limbic areas, 16 F males had elevated metabolic capacity relative to naïve and 3 F males, whereas no significant differences in brain metabolism were found between 3 F and naïve males. Behavioral differences were also found between 3 F and 16 F males. In a second experiment, we assessed differences in brain metabolism between sexually active and inactive males given only one opportunity to copulate and found no significant difference in neural metabolism between these males. This suggests that the differences found in the first experiment were primarily driven by differences in repeated experience rather than by sexual performance between 16 F and 3 F males. We speculate that these changes in brain metabolic capacity could be related to immediate early gene expression during copulation and could underlie the long-term behavioral changes accompanying heterosexual social experience.

Animals↗

PubMed2002

Impaired metabolic capacity in the perirhinal and posterior parietal cortex lead to dissociation between attentional, motivational and spatial components of exploration in the Naples High-Excitability rat.

This study aimed at investigating the neural substrates of spatial and non-spatial Behavioural components of exploration to novelty by a neurogenetic approach. Thus, functional imaging and Behavioural analysis were carried out in the Naples High-Excitability (NHE) rats, a model of hyperactivity and attention-deficit. Quantitative cytochrome oxidase (C.O.) histochemistry was used to measure the basal metabolic capacity of different forebrain structures. In parallel experiments, exploration in an 8-arm radial maze (Olton-maze) with extra-maze cues was used to measure attentional, motivational and spatial components of Behaviour after feeding rats' ad-libitum or at a reduced diet. Functional imaging analysis: brains from naive rats were stained for quantitative C.O. histochemistry along with standards. NHE rats showed lower C.O. activity in perirhinal and posterior-parietal cortex (all layers) and cortical amygdala, and greater activity in entorhinal cortex (superficial layers). The outer granular cell layer of the dentate gyrus had greater activity in NHE. Behavioural analysis: at low and high motivational level, maze exploration was reinforced during shaping throughout and then only a single arm. The Behaviour was monitored by a CCD camera and videotaped. (i) There was no line difference in working memory during non reinforced maze exploration, independent of the motivational level; (ii) during shaping with all baited arms, there was no line difference in working memory, but NHE rats showed a very low or lower food consumption at low and high motivational level, respectively; (iii) rats showed a higher working memory in finding the single baited arm at high motivational level; (iv) NHE rats paid little attention towards reinforcement upon visiting the baited arm only at low motivational level. Thus, Behavioural and functional neuroimaging analysis suggests the neural substrates of spatial and non-spatial components of exploration to be underlined by different network operations in the neocortical and limbic cortices in the NHE rat lines. Therefore, they appear as an useful tool to the understanding of Attention-Deficit Hyperactivity Disorder (ADHD) in children.

Animals↗

PubMed2002

Heterosexual housing increases the retention of courtship behavior following castration and elevates metabolic capacity in limbic brain nuclei in male whiptail lizards, Cnemidophorus inornatus.

In male vertebrates the display of courtship behavior depends on the presence of testicular androgens. However, social experiences in adulthood can alter the hormonal dependence of courtship behavior in a variety of species, and we have previously proposed that these behavioral changes are linked to changes in neural metabolic capacity (cytochrome oxidase activity). Here we investigated the effects of prior social experience (housing with females vs housing in isolation) on the retention of courtship behavior following gonadectomy and on cytochrome oxidase (CO) activity in male little striped whiptail lizards, Cnemidophorus inornatus. In Experiment 1, we found that males that were previously housed with females (HWF males) continued to display courtship behavior longer after castration than males previously housed in isolation (ISOLATE males). This is similar to the behavioral plasticity found in rodents and cats. On the other hand, courtship behavior while gonadally intact was indistinguishable between HWF and ISOLATE males. Because all males were housed individually following castration, the difference is due to different social experiences prior to castration. In Experiment 2, we found that gonadally intact HWF males had significantly elevated CO activity in the preoptic area, amygdala, and anterior and ventromedial hypothalamic areas relative to intact ISOLATE males. No significant differences in metabolism were found in the lateral septum, lateral hypothalamus, and habenula or in hindlimb muscle, suggesting that the increase in metabolism is specific to brain nuclei involved in courtship behavior. Altogether, this demonstrates that elevations in metabolic capacity correlate with experience-dependent increases in robustness to castration.

Anesthesia↗

PubMed2002

Effects of image resolution on autoradiographic measurements of posterior cingulate activity in PDAPP mice: implications for functional brain imaging studies of transgenic mouse models of Alzheimer's Disease.

Fluorodeoxyglucosepositron emission tomography (PET) studies find that persons with Alzheimer's disease have preferential reductions in posterior cingulate activity. Using fluorodeoxyglucose autoradiography, we found that transgenic mice overexpressing a mutant form of the human amyloid precursor protein have preferentially reduced activity in the same region, providing a potential brain imaging indicator of Alzheimer's disease in these animals. In this study, we considered the feasibility of using in vivo imaging techniques, such as PET, to detect this reduction despite their limitations in spatial resolution. Autoradiographic measurements of posterior cingulate activity were remeasured in the previously studied PDAPP transgenic and littermate control mice after the images were filtered to lower spatial resolutions. We continued to detect significantly lower cingulate activity in the transgenic mice when the images were blurred to 0.50 mm, failed to detect significantly abnormal activity when the images were blurred to 0.75 mm, and, indeed, found significantly higher activity when the images were blurred to 1.0 mm. Reversal in direction of the abnormality appears attributable to a previously observed truncation in the corpus callosum in PDAPP mice. With the possible exception of future in vivo imaging techniques that have a spatial resolution greater than or equal to 0.50 mm and high sensitivity, noninvasive functional brain imaging techniques like PET may not be suitable for detecting declines in regional activity in PDAPP mice. It remains possible that these imaging techniques will prove useful in transgenic mouse lines that do not exhibit the same morphological abnormalities in neighboring white matter regions.

Alzheimer Disease↗

PubMed2002

Dissociation of septo-hippocampal metabolism in the congenitally helpless rat.

Congenitally helpless rats, selectively bred to model features of endogenous depression, appear to have a paraventricular hypothalamic nucleus (PVH) that is markedly hyperactive. This study investigated septal and hippocampal regions purported to regulate the PVH. We found that cytochrome oxidase, an index of oxidative metabolism and neural activity, was significantly elevated in the hippocampus and subiculum of congenitally helpless rats. However, reduced activity was observed in the lateral and medial septal nuclei, the nucleus of the diagonal band, and the bed nucleus of the stria terminalis. This dissociation between hippocampal and septal activity may be a predisposing factor for the development of helpless behavior.

Animals↗

PubMed2001

Hypermetabolism of paraventricular hypothalamus in the congenitally helpless rat.

The congenitally helpless rat, selectively bred to model behavioral features of depression, has shown metabolic activity patterns in frontal and cingulate cortex similar to those detected in human imaging studies of depression and sadness. This study extends the same metabolic mapping technique (quantitative cytochrome oxidase histochemistry) to the hypothalamus, where activity levels were assessed in six nuclei: paraventricular nucleus, medial preoptic area, lateral hypothalamic area, supraoptic nucleus, suprachiasmatic nucleus, and ventromedial nucleus. Helpless rats were compared with a strain of non-helpless rats selectively bred for stress resistance. Only the paraventricular nucleus showed a significant group difference, with helpless rats showing elevated metabolism and non-helpless rats showing reduced metabolism relative to normal rats. Thus, paraventricular nucleus activity may be associated with genetic susceptibility to helpless behavior.

Animals↗

PubMed2001

Reduced corpus callosum, fornix and hippocampus in PDAPP transgenic mouse model of Alzheimer's disease.

Persons with Alzheimer's disease (AD) have progressive reductions in the relative sizes of the corpus callosum and hippocampus. Homozygotic PDAPP transgenic mice over-expressing a mutant form of the human amyloid precursor protein have more pronounced reductions in these regions, which are apparent prior to the deposition of amyloid plaques and do not progress with advancing age. The length of the corpus callosum was reduced by two-thirds, the fornix commissure was negligible, and the hippocampal volume was reduced by one-third, suggesting a massive disconnection between the cerebral hemispheres and the hippocampi in PDAPP mice. These findings, which might account for the early, nonprogressive behavioral abnormalities observed in these animals, have implications for the study of AD.

Alzheimer Disease↗

PubMed2001

Energy hypometabolism in posterior cingulate cortex of Alzheimer's patients: superficial laminar cytochrome oxidase associated with disease duration.

Among brain regions affected in Alzheimer's disease (AD), the posterior cingulate shows the earliest and largest decrement in energy metabolism. Positron emission tomography (PET) studies have shown that these decrements appear before the onset of memory deficits or other symptoms in persons at genetic risk for AD. This study compares in vivo imaging results and in situ postmortem analyses by examining the posterior cingulate (area 23) in 15 AD patients and 13 age-matched nondemented controls using quantitative cytochrome oxidase histochemistry as an intracellular measure of oxidative energy metabolic capacity. Each of the six layers of the posterior cingulate demonstrated a decline in cytochrome oxidase activity in AD relative to controls, whereas adjacent motor cortex showed no significant differences. This decrement did not appear to be mainly secondary to nonspecific decrement in mitochondrial enzymes, oxidative stress, cell loss, or histopathology. The cytochrome oxidase decrement was most severe in the superficial layer I (-39%), which demonstrated a correlation to disease duration. Covariance analyses suggest that superficial laminas undergo a functional uncoupling from the deeper layers of posterior cingulate cortex in AD, whereas no such effects are found in motor cortex or controls. These findings expand on previous results from PET studies by illuminating the layer-specific cytochrome oxidase contributions to energy hypometabolism. The findings suggest a decrement of cytochrome oxidase in posterior cingulate cortex, with progressive reduction within the superficial laminas linked to disease duration. Such decrement could contribute to some of the behavioral symptoms displayed by AD patients. This decrement appeared greater in women.

Age Factors↗

PubMed2001

Maturation of extinction behavior in infant rats: large-scale regional interactions with medial prefrontal cortex, orbitofrontal cortex, and anterior cingulate cortex.

The ability to express a behavior during the postnatal period may be related to developmental changes in the recruitment of particular neural systems. Here, we show that developmental changes in the functional interactions involving three cortical regions (the medial prefrontal cortex, orbitofrontal cortex, and anterior cingulate cortex) are associated with maturation of extinction behavior in infant rats. Postnatal day 17 (P17) and P12 pups were trained in a straight-alley runway on an alternating schedule of reward and nonreward [patterned single alternation (PSA)] or on a pseudorandom schedule of partial reinforcement (PRF); the pups were then injected with fluorodeoxyglucose (FDG) and shifted to continuous nonreward (extinction). Handled control groups exposed to the same training environment but not trained on a particular schedule were included. Among P17 pups, extinction proceeded faster in PSA pups relative to PRF pups. No differences were found between P12 groups. FDG uptake, an index of acute changes in functional activity, was quantified in the three cortical regions and 27 other brain regions of interest. A multivariate covariance analysis, seed partial least squares, revealed that functional relationships involving the three cortical regions and large-scale systems of regions throughout the rostrocaudal extent of the brain changed with training in P17 pups. The cortical regions were primarily uncoupled in the younger group. The data suggest that functional maturation of the frontal cortical regions and their interactions with other brain systems are related to the maturational shift in behavior.

Aging↗

PubMed2001

Metabolic mapping of brain regions associated with behavioral extinction in preweanling rats.

Fluorodeoxyglucose autoradiography, quantitative image analysis, and a multivariate tool (partial least squares) were used to assess distributed patterns of brain activation in postnatal day 17 and day 12 rat pups engaged in extinction of instrumental behavior. Pups were trained in a straight alley runway on an alternating reward schedule, or on a pseudorandom reward schedule, injected with fluorodeoxyglucose, and then shifted to continuous nonreward (extinction). Another group at each age served as handled controls. Day 17 pups trained on the alternating schedule demonstrated faster extinction rates compared to those trained on the pseudorandom schedule, a phenomenon known as the partial reinforcement extinction effect. No differences were found between day 12 groups. Partial least-squares analysis revealed age-related increases in fluorodeoxyglucose uptake across all three training conditions in the cingulate and frontal cortices, amygdala, midline thalamic nuclei, cerebellum, and in several brainstem regions. Training-related increases common to both age groups were found in the orbital frontal cortex, limbic thalamus, gigantocellular reticular nucleus, the somatosensory system, and cerebellum. Age-dependent training effects were found in the interpositus and medial cerebellar nuclei wherein fluorodeoxyglucose uptake increased in the day 12 alternation and pseudorandom groups relative to controls. Day 12 pups trained on the alternating schedule demonstrated increased uptake in the anterior dorsal thalamus relative to pseudorandom and control pups. Hence, a large-scale neural system comprised by somatosensory, cerebellar, and brainstem regions govern extinction behavior in preweanling rats. Recruitment of limbic structures may allow the older pups to modify extinction behavior based on prior learning.

Age Factors↗

PubMed2001

Effects of chronic sodium azide on brain and muscle cytochrome oxidase activity: a potential model to investigate environmental contributions to neurodegenerative diseases.

Deficits in oxidative phosphorylation have been implicated in many neurodegenerative diseases. In this study, cytochrome oxidase activity was inhibited following a 28-d systemic administration of nonlethal sodium azide via subcutaneous osmotic pumps. Quantitative enzyme histochemistry was performed on tissue sections from brain, skeletal muscle, and heart to localize cytochrome oxidase activity both globally and in regions within each tissue. Significant decreases of cytochrome oxidase activity were found in the brain and skeletal muscle but not heart. In addition, regions within each tissue were also analyzed, such as cortex and striatum in the brain and red and white fibers in skeletal muscle. The tissue specific inhibition of cytochrome oxidase by sodium azide could serve as a positive control for studies of other mitochondrial toxins in aerobically compromised cells. Therefore, chronic nonlethal sodium azide administration may provide a potential rat model for the study of mitochondrial dysfunction and the role of environmental pollutants in brain and muscle tissues affected in certain neurodegenerative diseases.

Analysis of Variance↗

PubMed2001

Associative effects of Pavlovian differential inhibition of behaviour.

The associative inhibitory control of behaviour is a major component of Pavlovian learning theory, but little is known about its functional neuroanatomy. The associative effects of differential inhibition of conditioned behaviour were investigated by mapping learning-related changes in brain activity of the rat with fluorodeoxyglucose autoradiography. Of interest was how a tone is processed in auditory and extra-auditory systems of the rat brain under similar behavioural, but different associative conditions. Conditioned emotional suppression to drink was used to assess training, and summation tests were used to verify that the tone became an inhibitor of conditioned behaviour. In the Inhibitor group, presentations of a tone stimulus alone were intermixed with presentations of a light stimulus followed by footshock. In the Pseudorandom group, the same numbers of tone, light and footshock presentations were used, but they were presented in a pseudorandom fashion. After training, fluorodeoxyglucose uptake was measured during tone presentations. Behavioural responding to the tone was similar during fluorodeoxyglucose uptake in the two groups, yet associative effects were found in brain activity. In the auditory system, the tone produced reduced fluorodeoxyglucose uptake in major relay nuclei (cochlear nucleus and inferior colliculus) in the Inhibitor group relative to the Pseudorandom group. The tone inhibitor produced similar decreases in the septohippocampal system and the retrosplenial cortex. In contrast, the tone inhibitor produced activity increases in somatosensory and reticulocerebellar systems. The findings provide the first detailed map of neural regions involved in the learned associations controlling differential inhibition of conditioned behaviour.

Acoustic Stimulation↗

PubMed2001

Mapping Pavlovian conditioning effects on the brain: blocking, contiguity, and excitatory effects.

Pavlovian conditioning effects on the brain were investigated by mapping rat brain activity with fluorodeoxyglucose (FDG) autoradiography. The goal was to map the effects of the same tone after blocking or eliciting a conditioned emotional response (CER). In the tone-blocked group, previous learning about a light blocked a CER to the tone. In the tone-excitor group, the same pairings of tone with shock US resulted in a CER to the tone in the absence of previous learning about the light. A third group showed no CER after pseudorandom presentations of these stimuli. Brain systems involved in the various associative effects of Pavlovian conditioning were identified, and their functional significance was interpreted in light of previous FDG studies. Three conditioning effects were mapped: 1) blocking effects: FDG uptake was lower in medial prefrontal cortex and higher in spinal trigeminal and cuneate nuclei in the tone-blocked group relative to the tone-excitor group. 2) Contiguity effects: relative to pseudorandom controls, similar FDG uptake increases in the tone-blocked and -excitor groups were found in auditory regions (inferior colliculus and cortex), hippocampus (CA1), cerebellum, caudate putamen, and solitary nucleus. Contiguity effects may be due to tone-shock pairings common to the tone-blocked and -excitor groups rather than their different CER. And 3) excitatory effects: FDG uptake increases limited to the tone-excitor group occurred in a circuit linked to the CER, including insular and anterior cingulate cortex, vertical diagonal band nucleus, anterior hypothalamus, and caudoventral caudate putamen. This study provided the first large-scale map of brain regions underlying the Kamin blocking effect on conditioning. In particular, the results suggest that suppression of prefrontal activity and activation of unconditioned stimulus pathways are important neural substrates of the Kamin blocking effect.

Acoustic Stimulation↗

PubMed2000

Congenital helpless rats as a genetic model for cortex metabolism in depression.

The validity of congenital helplessness as a genetic rat model for human depression was investigated in cortical regions of the rat brain thought to be analogous to those showing abnormalities in human neuroimaging studies. Cortex metabolism was analyzed using quantitative cytochrome oxidase histochemistry. Congenital helpless rats showed changes in frontal and cingulate regions comparable to those that have demonstrated metabolic differences in human depression. Significant metabolic decreases were found in dorsal frontal, medial orbital, and anterior cingulate, whereas a significant increase was found in infraradiata (subgenual) cingulate. The direction of these changes were the same as those seen in human studies. These findings support the validity of congenital helplessness as a model for human depression.

Animals↗

PubMed2000

Tracking Alzheimer's disease in transgenic mice using fluorodeoxyglucose autoradiography.

While transgenic mice have great promise in the study of Alzheimer's disease (AD), uncertainties remain about the extent to which they provide a model of the disorder or the best way to characterize disease progression. Using fluorodeoxyglucose (FDG) autoradiography, we found that transgenic mice over-expressing a mutant form of the human amyloid precursor protein have preferentially and progressively reduced activity in the posterior cingulate cortex and relatively spared activity in visual cortex, sensorimotor cortex, cerebellum and brain stem, a pattern previously demonstrated in FDG PET studies of persons with Alzheimer's disease, Brain imaging of posterior cingulate activity could provide an indicator of AD in suitable animals, helping to clarify disease mechanisms and screen candidate treatments.

Age Factors↗

PubMed2000

Network operations revealed by brain metabolic mapping in a genetic model of hyperactivity and attention deficit: the naples high- and low-excitability rats.

Genetic rat models are important for research on the neural networks of attention and emotionality. Naples-High Excitability (NHE) rats and Naples Low-Excitability (NLE) rats were investigated with random-bred (NRB) rats as controls. These rat lines were named for their respective behavior on spatial novelty tasks. Quantitative cytochrome oxidase (CO) histochemistry has been demonstrated to reflect long-lasting changes in tissue metabolic capacity. CO metabolic differences between the NLE and NHE were found in the granular cell layer of the outer blade of the dentate gyrus. In addition, NLE showed greater CO activity than NRB in medial frontal cortex, and lower activity in perirhinal cortex (dorsal region). NHE showed greater CO activity than NRB in entorhinal cortex (superficial layers) and lower activities in perirhinal cortex and cortical amygdala. These data support the hypothesis that NLE/NHE rats may be an appropriate model for studying genetically altered limbic regions related to impaired emotional processing. The results support the involvement of limbic circuits in attentive processes and impulsiveness, and support the use of the NLE and NHE strains as animal models of Attention Deficit Hyperactivity Disorder (ADHD) in children.

Animals↗

PubMed2000

Functional connectivity among limbic brain areas: differential effects of incubation temperature and gonadal sex in the leopard gecko, Eublepharis macularius.

The neural basis of individual differences in behavior has been studied primarily by analyzing the properties of specific neural areas. However, because of the organization of the nervous system, it is also plausible that differences in behavior are mediated by differences in the interactivity or functional connectivity among brain nuclei in particular neural circuits. In the leopard gecko, Eublepharis macularius, the temperature of the egg during incubation not only determines gonadal sex, but also shapes the sociosexual behaviors, reproductive physiology, and hormone sensitivity of adult animals. In this study the effects of both incubation temperature and gonadal sex on functional connectivity among limbic brain areas were examined. Functional connectivity was assessed by analyzing covariance patterns in metabolic capacity, as revealed by quantitative cytochrome oxidase histochemistry. It was hypothesized that incubation temperature and gonadal sex affect the propensity to display aggressive or sexual behaviors by altering the functional connectivity within relevant neural circuits. The correlations of metabolic capacity between the anterior hypothalamus and both the septum and preoptic area were significant only in relatively aggressive individuals, suggesting that these circuits may regulate the phenotypic variation in aggressiveness caused by incubation temperature. The correlations between the ventromedial hypothalamus and both the dorsal ventricular ridge and septum were significant only in females, suggesting that these circuits may modulate female-typical sexual behaviors. Correlations among preoptic, hypothalamic and amygdalar areas tended to be distributed across both sexes, suggesting that there may be shared pathways underlying the expression of male-typical and female-typical behaviors.

Aggression↗