Biomedical subjects

F Gonzalez-Lima

Publications and source records attributed to F Gonzalez-Lima.

At least 73 records · Page 4Linked to original sources

PubMed1994

Cytochrome oxidase activity in the auditory system of the mouse: a qualitative and quantitative histochemical study.

Detailed qualitative and quantitative determinations of cytochrome oxidase activity in the central auditory system of BALB/cJ mice were obtained at the light microscopic level. Cytochrome oxidase activity was determined using quantitative densitometry calibrated with standards of spectrophotometrically assayed enzymatic activity. This was done together with a cobalt-intensified histochemical procedure using fresh-frozen brains without perfusion-fixation. The resulting method showed improved sensitivity and allowed quantification of histochemical labeling as actual enzyme activity units. Adjacent sections were processed for either Nissl, fiber or Golgi stains to correlate the histochemical labeling with tissue morphology. The more peripheral auditory nuclei showed primarily somatic labeling with specific cell types showing predominant reactivity. However, higher auditory structures, including the inferior colliculus, medial geniculate and auditory cortex, showed predominantly neuropil reactivity. Comparison of mean cytochrome oxidase activities for the 27 auditory regions quantified revealed a trend for decreasing activity from the brainstem to the forebrain in central lemniscal structures. The extra-lemniscal auditory regions at each level showed lower activity than the corresponding lemniscal regions. The regions with the higher activity values showed around 10 times the labeling density of the white matter, indicating the high sensitivity of the method. The darkly labeling auditory structures were clearly delineated from surrounding neural regions, supporting the concept that basal levels of oxidative metabolic capacity are larger for the auditory system. It was concluded that the quantitative approach to cytochrome oxidase histochemistry may be applied successfully to the mouse brain. The normative data presented may be used as a starting point for other investigations of the effects of experimental manipulations on the metabolic activity of the auditory system.

Animals↗

PubMed1994

Network interactions among limbic cortices, basal forebrain, and cerebellum differentiate a tone conditioned as a Pavlovian excitor or inhibitor: fluorodeoxyglucose mapping and covariance structural modeling.

1. The objective was to examine how opposite learned behavioral responses to the same physical tone were differentiated by the pattern of interactions between extraauditory neural regions. This was pursued using a new approach combining behavior, neuroimaging, and network analysis to integrate information about differences in regional activity with differences in the covariance relationships between brain areas. 2. A tone was used as either a Pavlovian conditioned excitor or inhibitor. Rats were conditioned with reinforced trials of a conditioned excitor (A+) intermixed with nonreinforced trials of a tone-light compound (AX-). The tone was the excitor (A+) for the tone-excitor group and was the inhibitor (X-) for the tone-inhibitor group. After conditioning, all rats were injected with [14C(U)]2-fluoro-2-deoxyglucose (FDG) and presented with the same tone. 3. FDG autoradiography was used to measure regional activity and to generate interregional correlations of activity resulting from the presentation of the tone. A stepwise discriminant analysis was used to select brain regions that differentiated the excitor from the inhibitor effects. 4. Network analysis consisted of constructing an anatomic model of the brain regions, selected by the discriminant analysis, linking the regions with their known anatomical connections. Then, functional models for the tone-excitor and -inhibitor groups were constructed using structural equation modeling. Correlations of activity between regions were decomposed to calculate numerical weights, or path coefficients, for each anatomic path. These path coefficients were used to compare the interactions for the tone-excitor and -inhibitor models. 5. Regional differences in FDG uptake were found in the sulcal frontal cortex (SFC), lateral septum (LS), medial septum/diagonal band (MS/DB), retrosplenial cortex (RS), and dentate-interpositus nuclei of the cerebellum (DEN). Discriminant analysis selected three other regions that significantly discriminated the tone-excitor and -inhibitor groups: perirhinal cortex (PRh), nucleus accumbens (ACB), and the anteroventral nucleus of the thalamus (AVN). 6. Structural equation modeling identified two functional circuits that differentiated the groups. One involved the basal forebrain regions (LS, MS/DB, ACB) and the other limbic thalamocortical structures (SFC, RS, PRh, AVN). Differences in the interactions within these circuits were mainly in sign of the covariance relationships between regions, from positive for the tone-excitor model to negative path coefficients for the tone-inhibitor model. The path coefficient between the basal forebrain circuit and the limbic thalamocortical circuit showed the largest magnitude difference. This quantitative difference was mediated by a path from the MS/DB to PRh.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

Network analysis of functional auditory pathways mapped with fluorodeoxyglucose: associative effects of a tone conditioned as a Pavlovian excitor or inhibitor.

The purpose of this study was to examine how opposite learned associative properties of the same auditory stimulus are represented by the pattern of network interactions between auditory system structures. [14C(U)]2-fluoro-2-deoxyglucose (FDG) autoradiography was used to compare mean auditory system activity and interregional correlations resulting from the presentation of a tone trained as either a Pavlovian conditioned excitor or inhibitor. Rats were trained with reinforced trials of the conditioned excitor (A+) intermixed with non-reinforced trials of a tone-light compound (AX-). For the Conditioned Excitor group, the tone was the excitor (A+), while for the Conditioned Inhibitor group the tone was the inhibitor (X-). After conditioning, both groups were injected with FDG and presented with the same tone. Structural equation models, constructed from the anatomical connections between auditory regions and their interregional correlations in FDG uptake, were used to calculate path coefficients representing the network interactions. The opposite associative significance of the tone was reflected as functional changes in the interactions between parallel auditory pathways. Direct covariance effects through lemniscal pathways from the ventral cochlear nucleus were similar in absolute magnitude but differed in sign between the Excitor and Inhibitor network models. Extra-auditory influences on the dorsal cochlear nucleus were greater for the tone-inhibitor, reflecting possible interactions of this nucleus with extra-auditory regions. The different associative effects of the tone suggest that central auditory pathways can code not only the physical qualities, but also the associative significance of auditory stimuli. These findings demonstrate that neural network interactions differentiate the associative effects of tones in the brain. It is proposed that associative learning is a distributed property of neural networks and that such a property can be understood by considering the interactions between component parts of the network.

Acoustic Stimulation↗

PubMed1993

Functional mapping of the rat brain during drinking behavior: a fluorodeoxyglucose study.

Autoradiographic techniques using the radiolabeled glucose analog [14C]2-fluoro-2-deoxy-D-glucose (FDG) were used to map the functional activity in the CNS during drinking behavior. Rats were trained to drink water during a 1-h session each day. Half of the rats were injected with FDG and allowed to drink, while the other half were satiated prior to FDG injection. Uptake of FDG for drinking and control groups of rats was quantified in 60 brain structures from frontal cortex to cervical spinal cord. The largest percent increase in activity (96%) during drinking was in the lateral hypothalamus. Limbic structures with significant metabolic increases included the lateral septum (48%), lateral habenula (44%), and nucleus accumbens (32%). Thalamic nuclei activated included intralaminar (60%), zona incerta (51%), ventroposteromedial (50%), anterior ventral (47%), and dorsal medial (40%). Other structures with increases were the caudal caudate nucleus (53%) and the spinal trigeminal nucleus (45%). The findings were interpreted in light of related metabolic mapping studies of the effects of orofacial stimulation, dehydration, ingestion, arousal, and reward. It was concluded that this FDG study revealed primarily the involvement of structures linked to rewarding and arousal components of motivated drinking behavior, as well as sensorimotor correlates of the orofacial stimulation. The findings provide the first comprehensive functional map of brain systems related to drinking behavior in adult animals.

Animals↗

PubMed1992

Structural modeling of functional visual pathways mapped with 2-deoxyglucose: effects of patterned light and footshock.

This paper describes the first application of structural modeling to the visual system. Structural modeling, or path analysis, is a mathematical method that allows for the quantification of the functional strengths of anatomical connections between the structures that form a neural system. The objective was to demonstrate how structural modeling can be used to determine the functional interrelationships between brain structures that form the visual system and how these interrelationships change under different conditions. Data were obtained from measures of 2-deoxyglucose uptake in the visual system of rats presented with either patterned light or darkness. The effects of arousing footshock on visual system operations were also investigated. Models based on the anatomical connections and the interregional correlations between metabolic activity data were used to determine path coefficients representing the magnitude of the influence of each directional path. Statistical evaluation of the models revealed that the dominant positive influences on visual system activity in the darkness were the tectocortical subsystem and the descending connections from secondary visual cortex. In the patterned light model, the total influence of the geniculocortical subsystem was higher than in the dark, and the tectocortical pathways showed both a reduction and a shift in the direction of effects. The models also revealed that the effects of footshock-induced arousal on visual system operations depended upon the visual environment and on extra-visual influences. The footshock led to an increase in the interaction of the two main subsystems at the level of connections between primary visual cortex and the lateral posterior nucleus, and a descending negative influence from the secondary visual cortex became dominant. The models are discussed in the context of conventional analyses to show how structural modeling allows for the determination of much more information about the functional interactions within the visual system of subjects under different experimental conditions.

Animals↗

PubMed1991

Metabolic activation of the rat visual system by patterned light and footshock.

Autoradiography with [14C]2-deoxy-D-glucose was used to examine metabolic changes in the visual system of hooded rats exposed to patterned light or to darkness following footshock. Primary retinorecipient structures (superficial layer of the superior colliculus and the dorsal lateral geniculate nucleus) showed a response to light but not to shock. Higher visual sites showed two different shock effects. First, in darkness the intermediate grey layer of the superior colliculus was suppressed by the shock. Second, in the lateral posterior nucleus and primary visual cortex, the footshock led to significant enhancement of the metabolic responses to the patterned light. The findings suggest that footshock-induced arousal has significant modulatory effects on the operations of higher visual centers of behaving rats.

Analysis of Variance↗

PubMed1991

Structural modeling of functional neural pathways mapped with 2-deoxyglucose: effects of acoustic startle habituation on the auditory system.

This paper describes the first application of structural modeling to neuroscience. Structural modeling (also known as path analysis) is a method to assess the relative impact of directional links in a system and how these interrelations may change under different conditions. The objective was to demonstrate how structural modeling can be used to determine the functional interrelationships between brain structures that form the auditory system. Using structural modeling, changes in auditory system 2-DG uptake were examined during long- and short-term habituation of the acoustic startle reflex. Models were based on the anatomical connections between central auditory system structures. Using functional 2-DG data, the correlations between these structures were calculated and numerical weights were computed for each anatomical link. The analysis revealed that the lemniscal path was dominant during short-term habituation, while during long-term habituation this influence was modified through extra-lemniscal pathways. The models are discussed in the context of previous findings to demonstrate how structural modeling can not only complement, but also extract more information from 2-DG mapping experiments.

Acoustic Stimulation↗

PubMed1991

Functional mapping of the rat brain during vocalizations: a 2-deoxyglucose study.

Autoradiographic [14C]2-deoxyglucose (2-DG) procedures were used to map the functional activity in the CNS during vocalizations elicited by electrical stimulation of the midbrain reticular formation (MRF) in behaving rats. Following injection of 2-DG, rats received MRF stimulation through stainless steel electrodes over 90 min. Yoked controls received 2-DG injection followed by playback of the recorded vocalizations. Relative differences in peak isotope uptake (gray/white matter ratios) in 22 structures related to vocalization were compared between the two groups. The major findings were localized to hypothalamus, midbrain and brainstem structures. Significant increases in 2-DG uptake were noted in the following structures in MRF stimulated rats: dorsolateral central gray (PAG), MRF, lateral hypothalamus (LH), ventromedial hypothalamus (VmH), paraventricular nucleus (PVN) and nucleus ambiguus (NA). Cortical structures were not activated during MRF stimulation. The PAG and NA are known to be important relays in the production of vocalizations. MRF stimulation, therefore, activates the motor output pathways for vocalization, but does not appear to activate cortical and limbic motivational centers.

Animals↗

PubMed1991

Quantitative histochemistry of cytochrome oxidase in rat brain.

A quantitative analysis of cytochrome oxidase (CO) activity in histochemically stained sections of rat brain was developed using tissue standards and computerized image processing. Standards of brain paste containing known amounts of CO were cryosectioned and stained under the same conditions as brain sections. The gray levels of the stain were converted to units of CO activity using a calibration curve derived from densitometric analysis of the standards. The technique yields reproducible quantitative values, has the superior anatomical resolution of histochemistry, and is compatible with autoradiography.

Animals↗

PubMed1990

Functional reorganization of neural auditory maps by differential learning.

A new perspective on neural mechanisms of learning is emerging from studies showing that some sensory maps in mature brains can be reorganized in response to conditioned stimuli. Autoradiography with [14C] 2-deoxy-2-fluoro-D-glucose was used to examine changes in the functional tonotopic organization of the rat inferior colliculus during differential Pavlovian conditioning. Metabolic comparisons of adjacent tonotopic maps were made within the same inferior colliculus. They showed that tonotopic maps were enhanced during differential learning of tones associated with an arousing stimulus. The findings support a concept of sensory learning that postulates a functional reorganization of sensory maps in adult brains.

Acoustic Stimulation↗

PubMed1989

Learning-related activation in the auditory system of the rat produced by long-term habituation: a 2-deoxyglucose study.

Autoradiography with [14C]2-deoxyglucose (2-DG) was used to examine the functional activity of the rat auditory system during long- and short-term habituation of the acoustic startle reflex. The data showed that presentation of the acoustic stimulus to long-term habituated rats resulted in a learning-related metabolic enhancement that was significantly greater than the response evoked by the same acoustic stimulus in the inexperienced rats. This enhancement was localized to brainstem and midbrain auditory nuclei and no significant changes occurred at thalamocortical levels of the auditory pathway. The largest difference in 2-DG uptake between long- and short-term habituated rats was in the lateral superior olivary nucleus (LSO). The LSO activation suggests that olivocochlear efferents may operate in a central feedback control of peripheral auditory input during long-term habituation. Findings of enhanced metabolism from the cochlear nuclei to the central nucleus of the inferior colliculus indicated that active processes of neuronal plasticity take place in the lower auditory system during long-term habituation. The results provide the first demonstration of how a nonassociative learning experience such as long-term habituation modifies the metabolic activity of the auditory system. The findings support the conclusion that auditory responses of behaving animals to acoustic stimuli are dependent not only on the physical parameters of a stimulus, but also on its learned behavioral significance.

Acoustic Stimulation↗

PubMed1989

Neural substrates for long-term habituation of the acoustic startle reflex in rats: a 2-deoxyglucose study.

Autoradiography with [14C]2-deoxyglucose was used to examine the functional activity of the rat brain during long- and short-term habituation of the acoustic startle reflex. Long-term habituated rats, when compared to short-term rats, showed an enhanced metabolic activation of the auditory system, with the exclusion of thalamocortical levels. Regional metabolic increases were also located within the cerebellum and its major input-output structures. In contrast, the midbrain reticular formation and its ascending thalamocortical activating system showed a widespread metabolic suppression. The findings provide the first map of structures in a mammalian brain with learning-related metabolic alterations dependent on long-term habituation.

Acoustic Stimulation↗

PubMed1988

Functional mapping of the brainstem during centrally evoked bradycardia: a 2-deoxyglucose study.

Autoradiographic 2-deoxy-[14C] glucose (2-DG) procedures were used to map the functional activity of the brainstem during bradycardia elicited in awake rats by stimulation of the deep mesencephalic nucleus of the midbrain reticular formation (MRF). Quantitative determinations of 2-DG uptake in 46 brainstem structures of MRF-stimulated rats were compared to those of control rats without stimulation. This paper is the first 2-DG study to map the brainstem structures involved in a heart rate response evoked by central stimulation. The structures activated in the midbrain, caudal to the stimulation site, are part of the reticular formation and the central gray. The greater focuses of labeling were concentrated on the lateral aspects of the deep mesencephalic nucleus and on the lateral divisions of the midbrain central gray. The remaining structures activated during bradycardia were all located in the caudal medulla. The largest increase was observed in the caudal nucleus ambiguus. Significant increases were also found in the dorsal motor nucleus of vagus and in the nucleus of the solitary tract. The region of the caudal inferior olive showed a small increase in 2-DG uptake, whereas structures like the raphe magnus and parvocellular reticular nucleus showed a tendency to reduce 2-DG uptake levels in the stimulated rat. It was concluded that bradycardia induced centrally by MRF stimulation may be mediated by well-defined brainstem descending pathways, direct and indirect, between the activated regions of the midbrain and the various medullary nuclei known to induce bradycardia upon electrical stimulation. The results suggest that the midbrain central gray and reticular formation may play a role as intermediates in an indirect hypothalamus-medullary circuitry for bradycardia. In addition, descending MRF information and afferent baroreceptor inputs appear to exert their inhibitory influences on heart rate via a common set of neuroanatomical substrates in the medulla.

Animals↗

PubMed1988

Antagonism of behavioral effects of bromocriptine by prolactin in female cats.

The effects of the dopaminergic agonist bromocriptine (BC) and exogenously administered prolactin (PRL) on the spontaneous behavior of female cats were investigated. The objective was to test whether BC-induced behavioral effects may be antagonized by PRL. BC (6 mg/kg ip) administration induced abnormal behaviors such as limb flicks, abortive grooms, head/body shakes, and hallucinatory-like behavior/escape as well as excessive grooming. PRL (5 mg/kg ip) administration induced biphasic changes in grooming. The first change was an increase in grooming frequency averaging 256% of baseline control values and lasting for 1 h. This change was followed by reductions in grooming of 75 and 82.5% below baseline during Hours 2 and 3 postinjection, respectively. Combined BC and PRL treatment antagonized the frequency of BC-induced motor effects such as limb flicks, abortive grooms, and head/body shakes. Limb flicks occurred nine times more often 2 h after BC alone than after BC and PRL. The combined treatment also antagonized the excessive grooming observed after separate administrations of BC and PRL. The observed interactions between PRL and BC behavioral effects support the notion that PRL may be an important modulator of dopamine-dependent motor behavior in female cats.

Animals↗

PubMed1987

Metabolite involvement in the behavioral effects of bromocriptine in cats.

There is a lag phase of 30-60 min before the onset of bromocriptine (BC) action. This delay may be necessary for the formation of active metabolites. The objective was to determine whether the abnormal behavioral effects induced by BC involve active hepatic metabolites. Thus, we studied the effect of an inhibitor of hepatic hydroxylation metabolism (SKF 525A) on the behavior of BC-treated cats. Experiments began after six weeks of habituation and involved i.p. injections of: (1) propylene glycol (drug vehicle); (2) SKF 525A (70 mg/kg); (3) BC (10 mg/kg); and (4) SKF 525A followed 30 min later by BC. Each cat received the four treatments with two weeks elapsing between consecutive experiments. The frequency of 12 behaviors was scored for 60 min after 1 h posttreatment. BC alone induced emergent behavioral changes (hallucinatory-like, limb flicks, abortive grooms) that were not observed following control injections (vehicle and SKF 525A). There was a complete elimination of BC-induced hallucinatory-like behavior/escape by SKF 525A pretreatment. Other emergent behaviors were similarly reduced but persisted in all cats. The large frequency of grooming induced by BC was significantly reduced. SKF 525A pretreatment was correlated with a significant increase in staring and quiet sitting and a failure of BC to increase activities such as rubbing, treading and kneading. But many other BC-induced behaviors showed no changes. The data demonstrated that particular BC-induced changes in cats are antagonized by SKF 525A. The behavioral suppression caused by SKF 525A is compatible with the involvement of active hepatic metabolites from BC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Midbrain reticular stimulation produces patterns of metabolic activation and suppression in the cerebellum and vestibular nuclei: a 2-deoxyglucose study.

Autoradiographic 2-deoxyglucose (2-DG) procedures were used to map the activity in the cerebellum and vestibular nuclei during electrical stimulation of the midbrain reticular formation (MRF) in unrestrained rats. The major finding was a large increase in 2-DG uptake observed in the flocculus of MRF-stimulated rats. The peak of labeling in the flocculus was greater than any other peak of labeling measured in the cerebellum of MRF-stimulated or control rats. Structures showing significant decreases in 2-DG uptake included the 3 deep cerebellar nuclei and the 3 vestibular nuclei. The most pronounced suppressive effects of MRF stimulation were on the medial and lateral vestibular nuclei. The changes in metabolic activity revealed by 2-DG provide a first anatomical demonstration of: the activating effects of MRF stimulation on the flocculus; and the suppressive effects of MRF stimulation on deep cerebellar and vestibular nuclei. The observed patterns of metabolic activation and suppression were correlated with the known electrophysiological properties of the structures affected by MRF stimulation. The findings are consistent with specific effects of MRF stimulation on floccular-vestibular-visual interactions that may be disruptive to learning functions such as adaptability of the vestibulo-ocular reflex. The effects of MRF stimulation on the deep cerebellar nuclei are also consistent with a potential disruption of somatomotor learning-related activities in these nuclei. The results support the existence of MRF mechanisms for the modulation of integrative sensory-motor functions in the cerebellum.

Animals↗

PubMed1986

Activation of substantia gelatinosa by midbrain reticular stimulation demonstrated with 2-deoxyglucose in the rat spinal cord.

The autoradiographic [14C]2-deoxyglucose (2-DG) method was used to map the descending effects of midbrain reticular stimulation on the rat cervical spinal cord. The stimulation evoked consistently a defensive 'freezing' reaction as well as a large and highly localized increase in 2-DG uptake in the substantia gelatinosa (SG) (Rexed laminae 2-3). No stimulus-induced changes in 2-DG uptake were produced in the other regions of the spinal cord. The findings represent the first anatomical demonstration of the activating effects of midbrain reticular stimulation on the spinal cord. They also support the concept of an integrative role for the SG in descending reticular control mechanisms at the spinal cord level.

Animals↗

PubMed1986

Classical conditioning of tone-signaled bradycardia modifies 2-deoxyglucose uptake patterns in cortex, thalamus, habenula, caudate-putamen and hippocampal formation.

The 2-[14C]deoxyglucose (2-DG) autoradiographic method was used to map metabolic activity in all telencephalic and diencephalic structures of the rat brain during and after classical conditioning. A trial was made of a 4-5 KHz frequency modulated tone (CS) paired with midbrain reticular stimulation (US). The unconditioned response was a rapid bradycardia elicited by the US. Alert rats were injected with 2-DG, placed in a sound-proof chamber, and subjected during 90 min to a given treatment: (1) the CS before conditioning, (2) the US alone, (3) the paired CS-US (acquisition), (4) the CS after conditioning (extinction), (5) the US prior to the CS (sensitization), (6) the unpaired CS-US (pseudoconditioning), (7) the CS after pseudoconditioning and (8) no stimulation. The prefrontal cortex showed discrete regions with enhanced 2-DG uptake during conditioning and pseudoconditioning. A columnar organization was well-defined in the posterior parietal cortex of rats subjected to CS-US pairing. The medial thalamus was greatly activated in all groups subjected to reticular stimulation. The dorsomedial nucleus showed its largest activation during conditioning. The lateral habenula and a caudal portion of caudate-putamen showed an overall increase in 2-DG uptake during conditioning. The hippocampal formation showed a specific pattern of metabolic activation during conditioning and after conditioning. A laminar densitometric analysis showed that 2-DG uptake was concentrated in a central band along the sides of the hippocampal fissure which corresponded to the molecular layers. Only this neuropil band of greater metabolic activity showed the learning-related changes. In addition, the hippocampal formation was the only nonauditory structure in the forebrain which clearly responded to the acquired signal value of the tone CS after conditioning. These changes revealed by 2-DG provide a first demonstration of forebrain substrates with localized metabolic alterations related to learning and reticular sensitization.

Animals↗