Cortex Of Rabbits Research Articles

Synthesis and affinity for serotonin and dopamine transporters of some benzophenone oxime ether derivatives

In a previous study, we reported the synthesis of several 3-(methylenaminoxymethyl)-substituted piperidine derivatives and their ability to interfere with the transmission mediated by biogenic amines. The present study describes the preparation of some new oxime derivatives and their capacity to inhibit serotonin (SERT) and dopamine (DAT) transporters expressed at the level of the rabbit cortex and the striatal membranes, respectively. All the compounds showed K i values in the micromolar range on both transporters.

Effects of Nonsteroidal Anti-Inflammatory Drugs on Prostacyclin and Thromboxane in the Kidney

Dose-response curves were obtained relating the effects of increasing amounts of aspirin, a nonselective cyclooxygenase (COX) inhibitor, and celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, on the concentrations of prostacyclin and thromboxane in renal cortex and medulla of rabbits. The concentrations of the two agonists (aspirin and celecoxib) which elicit a half-maximal response on the prostanoid concentration (EC₅₀) were compared. Additionally, controls for prostacyclin and thromboxane were related to values for the experimental groups. The EC₅₀ values for celecoxib were considerably lower than those for aspirin, indicating that celecoxib was more effective in suppressing prostanoid production. There were also significant differences between the majority of experimental groups and their respective controls, further evidence for the greater inhibitory activity of celecoxib on prostacyclin. Celecoxib lowered the ratio prostacyclin/thromboxane in the renal medulla; mercuric chloride further diminished the concentration of prostacyclin in the renal medulla. The results confirm that in the normal rabbit kidney, both nonselective and specific COX inhibitors interfere with renal prostanoid synthesis, but that a selective COX-2 inhibitor is more effective.

Dynamics of local changes and oscillations in energy metabolism in the rabbit cerebral cortex during the formation of a conditioned defensive reflex.

Brain energy metabolism associated with different functional states and different types of human and animal activity is accompanied by dynamic changes in the degree of linkage between glycolysis and oxidalive phosphorylation in different cell compartments. These processes are reflected in the redox state of brain tissue and can be recorded potentiometrically as changes in the redox state potential (E) of brain tissue. Studies of E in the cortex of rabbits using implanted platinum electrodes showed that during the acquisition of a conditioned defensive reflex using a combination of a light and a mild electric shock to one of the rabbit's ears, conical E showed oscillations with periods of several seconds after 5-15 combinations. This number of combinations started to be accompanied by generalized changes in E in the cortex, which, at 20-100 combinations, could be either an increase or a decrease in E. As the number of combinations increased, increases in E were gradually replaced by decreases. By 200-400 combinations, occillations in E disappeared and the episodes of decreased E accompanying combinations acquired a stable local character. These results suggest that there is a change in the balance of the major sources of brain tissue energy supply during the formation and stabilization of a conditioned defensive reflex: at the initial stages of acquisition of the conditioned reflex a number of conical points have an energy supply dominated by tissue respiration, while the main energy source for brain function during performance of the acquired conditioned defensive reflex is glycolysis.

Fast-spike interneurons and feedforward inhibition in awake sensory neocortex.

'Fast-spike' interneurons of layer 4 mediate thalamocortical feedforward inhibition and can, with some confidence, be identified using extracellular methods. In somatosensory barrel cortex of awake rabbits, these 'suspected inhibitory interneurons' (SINs) have distinct receptive field properties: they respond to vibrissa displacement with very high sensitivity and temporal fidelity. However, they lack the directional specificity that is clearly seen in most of their ventrobasal thalamocortical afferents. Several lines of evidence show that layer-4 SINs receive a potent and highly convergent and divergent functional input from topographically aligned thalamocortical neurons. Whereas the unselective pooling of convergent thalamocortical inputs onto SINs generates sensitive and broadly tuned inhibitory receptive fields, the potent divergence of single thalamocortical neurons onto many SINs generates sharply synchronous (+/-1 ms) activity (because of coincident EPSPs). Synchronous discharge of these interneurons following thalamocortical impulses will generate a synchronous feedforward release of GABA within the barrel. Thalamocortical impulses will, therefore, generate only a brief 'window of excitability' during which spikes can occur in the post-synaptic targets of fast-spike interneurons. This fast, synchronous, highly sensitive and broadly tuned feed-forward inhibitory network is well suited to suppress spike generation in spiny neurons following all but the most optimal feedforward excitatory inputs.

Distribution of behaviorally specialized neurons and expression of transcription factor c-Fos in the rat cerebral cortex during learning.

Studies of learning are now performed at very differentlevels, including the neuronal and molecular biological lev-els. Integration of data obtained at these two levels canfacilitate the development of overall concepts of processesoccurring in the brain during learning.Data obtained using neurophysiological methods pro-vide evidence that learning is mediated by a process of“behavioral specialization” of silent reserve neurons [1, 3,5, 7]. According to the systems-selection theory of the for-mation of a new behavioral act, learning involves the for-mation of a new functional system, i.e., systemogenesis; atthe neuronal level, this corresponds to the formation of neu-ron specializations for this system [7]. Neuron specializa-tion consists of the appearance of activation of previously“silent” neurons every time the relevant formed behavioralact takes place.It has repeatedly been demonstrated that differentbrain structures are characterized by different patterns ofbehavioral neuron specializations [1]. Thus, the motor cor-tex is dominated by neurons specialized with regard to sys-tems formed at the early stages of individual development:so-called old system neurons, for example, “movement”neurons or “food taking” neurons. The cingulate cortex isdominated by neurons specialized with regard to new sys-tems formed when animals learn in an experimental cage,for example, “pedal-pressing” neurons [4]. Comparison ofthe patterns of specialization in the retrosplenial area of thecingulate cortex and in the anterolateral area of the motorcortex in rabbits shows that the number of “new” neurons inthe former is an order of magnitude greater than in the lat-ter. It has also been demonstrated that the patterns of spe-cialization in the cingulate cortex are similar in rabbits andrats: “new” neurons predominate in both species [3]. Fur-ther studies reported by Gavrilov et al. have demonstrated asimilarity between the patterns of specialization in themotor cortex of rats and rabbits. Thus, the ratio of the pat-terns of neuron specializations in rats is the same as that inrabbits.The processes underlying the formation of neuron spe-cialization are evidently based on long-term changes in cellfunctions and cell connections, which must require activa-tion of gene expression. Learning has been shown to inducea cascade of molecular rearrangements in neurons, andexpression of early genes has been shown to be one of thecritical elements of these modifications [2]. Induction of thec-fos gene during formation of a new behavior, this beingone of the main members of the immediate early gene fam-ily, varies in different brain structures. Zhu et al. [9] haveestablished that the set of structures activated in the ratbrain, demonstrated by immunohistochemical mapping,coincides with the set of structures identified as activated byrecording of neuron activity during presentation of familiarand unfamiliar objects. These points suggest that differ-ences in the levels of gene expression between structuresmay be associated with the different contributions of thesebrain structures to the process of neuron specialization dur-ing learning. Confirmation of this suggestion and improve-ment of our understanding of the molecular biological basesof the formation of neuron specialization require compar-isons of the numbers of neurons expressing early genes in agiven brain structure during learning with the level ofinvolvement of that structure in the formation of new spe-

Thalamocortical control of feed-forward inhibition in awake somatosensory 'barrel' cortex.

Intracortical inhibition plays a role in shaping sensory cortical receptive fields and is mediated by both feed-forward and feedback mechanisms. Feed-forward inhibition is the faster of the two processes, being generated by inhibitory interneurons driven by monosynaptic thalamocortical (TC) input. In principle, feed-forward inhibition can prevent targeted cortical neurons from ever reaching threshold when TC input is weak. To do so, however, inhibitory interneurons must respond to TC input at low thresholds and generate spikes very quickly. A powerful feed-forward inhibition would sharpen the tuning characteristics of targeted cortical neurons, and interneurons with sensitive and broadly tuned receptive fields could mediate this process. Suspected inhibitory interneurons (SINs) with precisely these properties are found in layer 4 of the somatosensory (S1) 'barrel' cortex of rodents and rabbits. These interneurons lack the directional selectivity seen in most cortical spiny neurons and in ventrobasal TC afferents, but are much more sensitive than cortical spiny neurons to low-amplitude whisker displacements. This paper is concerned with the activation of S1 SINs by TC impulses, and with the consequences of this activation. Multiple TC neurons and multiple S1 SINs were simultaneously studied in awake rabbits, and cross-correlation methods were used to examine functional connectivity. The results demonstrate a potent, temporally precise, dynamic and highly convergent/divergent functional input from ventrobasal TC neurons to SINs of the topographically aligned S1 barrel. Whereas the extensive pooling of convergent TC inputs onto SINs generates sensitive and broadly tuned inhibitory receptive fields, the potent TC divergence onto many SINs generates sharply synchronous activity among these elements. This TC feed-forward inhibitory network is well suited to provide a fast, potent, sensitive and broadly tuned inhibition of targeted spiny neurons that will suppress spike generation following all but the most optimal feed-forward excitatory inputs.

Correlations between response properties of periodontal mechanosensitive neurones in the primary somatosensory cortex of the rabbit and cortically induced rhythmical jaw movements

The response properties of incisor- and molar-sensitive periodontal mechanosensitive (PM) neurones in the primary somatosensory (SI) cortex of rabbits were examined and rhythmical jaw movements induced by repetitive electrical stimulation of the recording sites of cortical PM neurones were observed. PM units were recorded from the rostromedial (RM) and rostrolateral (RL) areas of the SI cortex. In the RM area, most PMs (85%) were lower incisor-sensitive. Electrical stimulation of the RM area produced chopping-type rhythmical jaw movements. In the RL area, both incisor- and molar-sensitive PM units were recorded, and molar-sensitive units were located more rostromedially than incisor-sensitive units. More than half (66%) of the incisor-sensitive PM units were upper incisor-sensitive. The incidences of sustained-response type units were 8 and 10% for upper incisor- and lower incisor-sensitive units and 28 and 34% for upper molar- and lower molar-sensitive units, respectively. The optimal stimulus directions for the upper molar-sensitive units were predominantly labial or lingual, whereas those for most of the lower molar-sensitive units were lingual. Electrical stimulation of the PM unit-recording sites in the RL area induced grinding-type rhythmical jaw movements. Based on these findings, the lower incisor-sensitive neurones in the RM area of the SI cortex might mainly contribute to a neural network that controls jaw movements during ingestion. Furthermore, the response properties of molar-sensitive cortical neurones might be useful for discriminating the magnitude and direction of the biting force during grinding. Further studies are needed to clarify the role of upper incisor-sensitive neurones in the RL area in triggering grinding-type rhythmical jaw movements.

Classification of EEG patterns using nonlinear dynamics and identifying chaotic phase transitions

A dynamical classification method is introduced based on the principle of encoding sensory information in oscillating spatio-temporal patterns. The method is used for the evaluation of EEG signals measured by spatially distributed electrodes over sensory cortices of rabbits. Our analysis reveals two types of patterns in neocortex. One type occurs with short latency after stimulus arrival. This early pattern represents the direct impact of a discriminated stimulus on the receiving cortex. The other type is endogenous and occurs with variable latency in the subsequent ∼1200 ms . It represents the destabilization of the spatio-temporal dynamics of the cortices and consequent phase transitions.

Water diffusion in the rabbit lens in vivo.

To examine water diffusion in the crystalline lens and sugar cataracts in the rabbits in vivo. Water self-diffusion in the lens cortices of alloxan-diabetic and galactosemic rabbits was examined with magnetic resonance imaging (MRI). The animals were positioned in a 4.7-tesla animal system in conjunction with a 1-inch surface coil for the eye. Diffusion-weighted MRI was conducted using a pulsed-gradient spin-echo sequence with a gradient strength of 0-6 Gs/cm in the primary and secondary coordinates. Other MRI parameters included TR (repetition time)/TE (echo time) = 2,000/10 ms, a field of view of 4 cm, and a 256 x 128 matrix. There appeared an increase in water relaxation resulting in an increase of % (equatorial cortex depth)/(lens long axis) from 18 in the lenses of normal rabbits to 30.4 and 39.9 in the lenses of galactosemic and diabetic rabbits, respectively. In addition, water diffusion changed in the lens of the diabetic rabbit with an increasing intracellular fluidity along the long axis of the cortical fibers, for example, the diffusion coefficient changed from a normal of 0.48 to 0.96 x 10(-5) cm2 s-1 in the lens of the diabetic rabbit. These results showed altered water mobility due to subcellular disturbances occurring before any apparent lens opacities. Further, there also was an increase in the water diffusivity in the aqueous humor from a normal of 1.77 to 2.67 x 10(-5) cm2 s-1 in the galactosemic rabbit eye suggesting an increase in either free water proportion or thermal convection. Resistance to water self-diffusion appeared to relate to lens fiber orientation and intracellular protein order. Diffusion imaging therefore can be used to examine water self-diffusion to detect early osmotic alteration of lens fibers.

Electrical impedance tomography of human brain activity with atwo-dimensional ring of scalp electrodes

Previously, electrical impedance tomography (EIT) has been used to imageimpedance decreases in the exposed cortex of rabbits during brain activity.These are due to increased blood volume at the site of the stimulated cortex;as blood has a lower impedance than brain, the impedance decreases. Duringhuman brain activity similar blood flow changes have been detected usingpositron emission tomography (PET) and functional magnetic resonance imaging(fMRI). If blood volume also changes then the impedance of human cortex willchange during brain activity; this could theoretically be imaged with EIT. EITdata were recorded from a ring of 16 scalp electrodes in 34 recordings in 19adult volunteers before, during and after stimulation with (1) a visualstimulus produced by an 8 Hz oscillating checkerboard pattern or (2) sensorystimulation of the median nerve at the wrist by a 3 Hz electrical square wavestimulus. Reproducible impedance changes, with a similar timecourse to thestimulus, were seen in all experiments. Significant impedance changes wereseen in 21 ± 5% (n = 16, mean ± SEM) and 19 ± 3% (n = 18)of the electrode measurements for visual and somatosensory paradigmsrespectively. The reconstructed 2D EIT images showed reproducible impedancechanges in the approximate region of the stimulated cortex in 7/16 visualand 5/18 somatosensory experiments. This demonstrates that reproducibleimpedance changes can be measured during human brain activity. The finalimages contained spatial noise; the reasons for this and strategies to reducethis in future are discussed.

Spike responses of neurons in the motor area of the cortex of elderly rabbits to specific stimuli.

The spike responses of neurons in the motor area of the cortex to tactile and electrocutaneous stimulation of the forelimb were studied in elderly (aged 6-7 years) rabbits. In comparison with young rabbits, the cortex of adult animals contained fewer cells responding to afferent stimulation. The activatory responses of neurons in elderly animals showed smaller increases in the spike frequency from the baseline level. Long-latency, slow activatory responses, which were not characteristic of cortical neurons in young animals, appeared; the pattern of these responses could be partially corrected by administration of acetylcholine in the vicinity of the neurons being recorded. The parameters of inhibitory responses were enzyme of the significantly different in animals of different ages.

Analysis of spatial patterns of phase in neocortical gamma EEGs in rabbit.

Arrays of 64 electrodes (8 x 8, 7 x 7 mm) were implanted epidurally on the surface of the visual, auditory or somatosensory cortex of rabbits trained to discriminate conditioned stimuli in the corresponding modality. The 64 electroencephalographic (EEG) traces at all times displayed a high degree of spatial coherence in wave form, averaging >90% of the variance in the largest principal components analysis component. The EEGs were decomposed with the fast Fourier transform (FFT) to give the spatial distributions of amplitude and phase modulation (AM and PM) in segments 128 ms in duration. Spatial (2-dimensional) and temporal (1-dimensional) filters were designed to optimize classification of the spatial AM patterns in the gamma range (20-80 Hz) with respect to discriminative conditioned stimuli. No evidence was found for stimulus-dependent classification of the spatial PM patterns. Instead some spatial PM distributions conformed to the pattern of a cone. The location and sign (maximal lead or lag) of the conic apex varied randomly with each recurrence. The slope of the phase gradient varied in a range corresponding to that of the conduction velocities reported of axons to extend parallel to the cortical surfaces. The durations and times of recurrence of the phase cones corresponded to those of the optimally classified spatial AM patterns. The interpretation is advanced that the phase cones are manifestations of state transitions in the mesoscopic dynamics of sensory cortices by which the intermittent AM patterns are formed. The phase cones show that the gamma EEG spatial coherence is not due to volume conduction from a single deep-lying dipole generator nor to activity at the site of the reference lead on monopolar recording. The random variation of the apical sign shows that gamma AM patterns are self-organized and are not imposed by thalamic pacemakers. The half-power radius of the phase gradient provides a useful measure of the soft boundary condition for the formation and read-out of cooperative cortical domains responsible for binding sensory information into the context of prior experience in the process of perception.

Selective deafferentation of the rabbit cortex: A new animal model of Alzheimer's disease

Selective deafferentation of the rabbit cortex: A new animal model of Alzheimer's disease

Spatial orientation of the microscopic elements of cortical repair bone.

This study was designed to assess whether the original orientation of the elements of cortical diaphyseal bone is reestablished during 18 months of repair. Full thickness 3-mm drill holes were created surgically through the tibial and femoral cortices of adult rabbits and studied by light and polarizing microscopic analysis at 1, 4, 8, and 16 weeks and 6, 12, and 18 months after the defects were created. From 16 weeks to 12 months the defects were repaired fully with lamellar bone, while the longitudinal spatial orientation of the repair lamellae was at a distinct angle to that of the original bone. At 18 months, the internal organization of the major individual microscopic elements (osteons) were reconstituted in a manner similar to that of the original bone; however, the three-dimensional spatial orientation of the osteons in the repair bone relative to the long axis of the osteons of the adjacent original bone and of the bone removed to create the defect was not reestablished completely. The imperfect spatial disposition of the microscopic elements of bone tissue may contribute significantly to refracture of a long bone after removal of screws from plated or unplated long bone fractures.

Mating modifies c-fos expression in the brain of male and female rabbits

Copulation in rabbits provokes behavioral and neuroendocrine changes in both sexes. To investigate if the activity of particular brain regions is modified accordingly we quantified, by the reverse transcription-polymerase chain reaction method, c-fos expression in the preoptic area, hypothalamus, hippocampus, and frontal cortex of male and female rabbits before mating, immediately afterwards, and 1 h later. Mating immediately increased c-fos expression in the hypothalamus of both sexes, the frontal cortex of females, and the preoptic area of males. c-fos expression did not change in the hippocampus after mating in either sex but decreased in the preoptic area of females following mating. Results show that mating provokes changes in brain activity, in a gender- and region-specific manner, which may underlie the behavioral and endocrine consequences of copulation in rabbits.

Alterations of Alzheimer's disease in the cholesterol-fed rabbit, including vascular inflammation. Preliminary observations.

We determined the levels of endothelial inflammation using MECA-32 antibody and alpha 4 nicotinic receptor subunit densities employing [3H]epibatidine binding in the brains of Alzheimer's disease (AD) patients, cholesterol-fed rabbits, and appropriate controls. We also assessed rabbit brain for beta-amyloid levels and immunohistochemical localization, and for evidence of blood-brain barrier breach using normally-excluded Evans Blue dye. Dietary cholesterol induced a twofold increase in beta-amyloid concentration in rabbit hippocampal cortex, which may be related to the appearance of beta-amyloid immunoreactivity in the neuropil. Epibatidine binding was significantly decreased in AD superior frontal cortex, but unchanged in the superior frontal cortex of cholesterol-fed rabbits. Increased vascular MECA-32 immunoreactivity occurred in AD and cholesterol-fed rabbit brain. Evans Blue dye could be found in the parenchyma of cholesterol-fed rabbits only, and appeared as pockets of dye surrounding small blood vessels. The data suggest that vascular inflammation can lead to breach of the blood-brain barrier, which may produce biochemical derangements in surrounding brain tissue that are conducive to production of beta-amyloid.

GABAergic neurons in the rabbit visual cortex: percentage, layer distribution and cortical projections

GABAergic neurons were studied in the rabbit visual cortex to estimate their percentage and their proportion among projection neurons to area 17. To retrogradely label projection neurons furnishing cortico-cortical connections to area 17, WGA-HRP injections were given to the visual cortex of rabbits. To determine the general incidence of GABAergic neurons in the visual cortex and the proportion of GABAergic neurons to tracer-labelled cortico-cortical cells, GABA post-embedding immunocytochemistry was made on 1-μm-semithin sections. GABAergic neurons accounted for 15.2% in area 17 and 15.5% in area 18. Except for layer 1, the highest incidence per layer was 25% in layer 5 of area 17. Areas 17 and 18 were nevertheless similar to each other in the distribution of their GABAergic neurons among layers. GABAergic neurons of every layer were double-labelled as furnishing connections intrinsic to area 17. At layer 2/3 and at the border between layers 5 and 6, the intrinsic GABAergic neurons were double-labelled up to 2500 μm from the site of tracer injections. Notably, none of >6250 neurons yielding either callosal or inter-areal ipsilateral projections extrinsic to area 17 was GABAergic. Comparing these findings with those reported for other mammals, it seems that the incidence and distribution of GABAergic neurons in the visual cortex is similar in rabbits and rats. In contrast to rats but akin to higher mammals, no GABAergic neuron was found to furnish cortico-cortical connections to area 17 other than intrinsic connections.

Localization of epithelial sodium channel and aquaporin-2 in rabbit kidney cortex.

The amiloride-sensitive epithelial sodium channel (ENaC) and the vasopressin-dependent water channel aquaporin-2 (AQP2) mediate mineralocorticoid-regulated sodium- and vasopressin-regulated water reabsorption, respectively. Distributions of ENaC and AQP2 have been shown by immunohistochemistry in rats. Functional data from rabbits suggest a different distribution pattern of these channels than in rats. We studied, by immunohistochemistry in the rabbit kidney cortex, the distributions of ENaC and AQP2, in conjunction with marker proteins for distal segments. In rabbit cortex ENaC is restricted to the connecting tubule (CNT) cells and cortical collecting duct (CCD) cells. The intracellular distribution of ENaC shifts from the apical membrane in the most upstream CNT cells to a cytoplasmic location further downstream in the CNT and in the CCD cells. AQP2 is detected in the CCD cells exclusively. The anatomic subdivisions in the rabbit distal nephron coincide exactly with distributions of apical transport systems. The differences between rabbits and rats in the distribution patterns of ENaC and AQP2 may explain functional differences in renal salt and water handling between these species.

Cholinergic deafferentation of the rabbit cortex: a new animal model of Aβ deposition

Brain deposition of the amyloid beta-peptide (Abeta) is a critical step in the pathogenesis of Alzheimer's disease (AD) and human cerebral amyloid angiopathy (CAA). A small fraction of AD and CAA cases are caused by gene mutations leading to increased production and deposition of Abeta, but for the majority, there is no known direct genetic cause. We have hypothesized that Abeta deposition in these sporadic cases occurs as a result of cortical cholinergic deafferentation. Here we show that cortical cholinergic deafferentation, induced in rabbits by a selective immunotoxin, leads to Abeta deposition in cerebral blood vessels and perivascular neuropil. Biochemical measurements confirmed that lesioned animals had 2.5- and 8-fold elevations of cortical Abeta40 and Abeta42, respectively. Cholinergic deafferentation may be one factor that can contribute to Abeta deposition.

Inhibition of glutamine synthetase in rabbit pneumococcal meningitis is associated with neuronal apoptosis in the dentate gyrus.

Apoptosis of dentate granular cells in the hippocampal formation during bacterial meningitis may be mediated by glutamate toxicity. For this reason, we studied the relationship between glutamine synthetase activity and regional neuronal apoptosis in rabbits with experimental pneumococcal meningitis. The duration of meningitis was 24 h, and the treatment was started 16 h after infection. Significant increases of glutamine synthetase protein concentration (P < 0.05) were found in the frontal cortex of rabbits with meningitis (n = 7) and rabbits with meningitis receiving ceftriaxone treatment (n = 12) as compared to the control animals (n = 14). No significant differences were seen in the hippocampal formation. The enzymatic activity of glutamine synthetase also was elevated in the frontal cortex (P < 0.05), but not in the hippocampal formation of rabbits with meningitis. After intravenous administration of L-methionine sulfoximine (specific inhibitor of glutamine synthetase) in rabbits with meningitis treated with ceftriaxone (n = 10), the concentration of neuron-specific enolase in CSF (P = 0.025) and the density of apoptotic neurons in the dentate gyrus quantified with the in-situ tailing reaction (P = 0.043) were higher than in meningitic animals receiving only ceftriaxone (n = 10). In conclusion, the inability of hippocampal glutamine synthetase to metabolize excess amounts of glutamate may contribute to neuronal apoptosis in the hippocampal formation during meningitis.