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PubMed2004

Deficits in sensorimotor gating and tests of social behavior in a genetic model of reduced NMDA receptor function.

Reduced NMDA receptor function is hypothesized to contribute to the pathophysiology of schizophrenia. In order to model chronic and developmental NMDA receptor hypofunction, a mouse line was developed that expresses low levels of the NMDA R1 subunit (NR1) of the NMDA receptor. The present study tested the hypothesis that these NR1 hypomorphic mice would exhibit deficits in sensorimotor and conspecific interactions, analogous to deficits observed in schizophrenic patients. F1 hybrid mice homozygous for the NR1 hypomorphic mutation (NR1 -/-) were generated by crossing heterozygous mice (NR1 +/-) from C57BL/6 and 129 Sv/Ev backgrounds. To assess sensorimotor gating, mice were tested in the paradigm of prepulse inhibition of acoustic startle. The NR1 hypomorphic mice exhibited increased acoustic startle responses and also showed deficits in prepulse inhibition. Startle responses were differentially altered by predator odor exposure in the male NR1 -/- mice, in comparison to control mice. In a test of social affiliation, the wild type mice spent significantly more time investigating a novel mouse in comparison to the NR1 -/- mice. In a resident-intruder test, marked deficits were found in sex-specific aggressive behavior between the wild type and mutant mice. These data support the contention that the NR1 hypomorphic mice exhibit alterations in sensorimotor gating and typical conspecific interactions, reminiscent of behavioral disturbances associated with schizophrenia. The NR1 hypomorphic mice could represent a model system to explore novel treatment and preventative strategies for certain symptoms of schizophrenia.

Agonistic Behavior↗
PubMed2006

Behavioral recovery from unilateral photothrombotic infarcts of the forelimb sensorimotor cortex in rats: role of the contralateral cortex.

During sensorimotor recovery following stroke ipsi- and contralesional alterations in brain function have been characterized in patients as well as animal models of focal ischemia, but the contribution of these bilateral processes to the functional improvement is only poorly understood. Here we examined the role of the homotopic contralateral cortex for sensorimotor recovery after focal ischemic infarcts at different time periods after the insult. One group of animals received a unilateral single photothrombotic infarct in the forelimb sensorimotor cortex, while four additional groups received a second lesion in the contralateral homotopic cortex either immediately or 2 days, 7 days, or 10 days after the first infarct. The time course of functional recovery of the impaired forelimbs was assessed using different sensorimotor scores: forelimb-activity during exploratory behavior and frequency of forelimb-sliding in the glass cylinder as well as forelimb misplacement during grid walking. Focal infarcts in the forelimb sensorimotor cortex area significantly impaired the function of the contralateral forelimb in these different behavioral tests. The subsequent damage of the contralateral homotopic forelimb sensorimotor cortex only affected the forelimb opposite to the new lesion but did not reinstate the original deficit. The time course of sensorimotor recovery after bilateral sequential cortical infarcts did not significantly differ from animals with unilateral single lesions. These data indicate that following small ischemic cortical infarcts in the forelimb sensorimotor cortex the contralateral cortex homotopic to the lesion plays only a minor role for functional recovery.

Animals↗
PubMed2003

Behavioral transitions modulate hippocampal electroencephalogram correlates of open field behavior in the rat: support for a sensorimotor function of hippocampal rhythmical synchronous activity.

A clear relationship exists between moment-to-moment behavioral elements and hippocampal rhythmical synchronous activity (RSA) (theta rhythm). However, behavioral elements are not isolated events but are part of behavioral sequences in a context of behavioral activity. By concurrently monitoring open field behavior and hippocampal EEG, EEG correlates of open field behavior in relation to preceding and following behavior were studied in Sprague Dawley rats to determine whether the behavioral context influences EEG correlates of behavior. Results show that preceding and subsequent behavioral patterns influenced the spectral power correlates of behavior. RSA power was increased when a "type 1 behavior" (voluntary movement) preceded the behavior compared with when a "type 2 behavior" (automatic movement, awake immobility) preceded it. The modulating effect of behavioral transitions was shown for several types of behaviors, and systematic modulation of hippocampal EEG correlates of behavior was demonstrated. The present report shows that the strong and systematic relationship between hippocampal RSA and behavior is modulated by the behavioral-sequential context. Thus, in addition to the well established relationship between RSA and motor activity, a second nonmotor process seems to contribute to hippocampal RSA. A likely candidate is a sensory process, which is in accordance with theories on the sensorimotor function of hippocampal RSA.

Animals↗
PubMed2004

Role of the pedunculopontine tegmental nucleus in sensorimotor gating and reward-related behavior in rats.

RATIONALE: The pedunculopontine tegmental nucleus (PPTg) is involved in the execution and regulation of a variety of behaviors. Most investigations used brain lesions that have certain disadvantages, such as functional compensation over time. OBJECTIVES: In the present study, we investigated by temporary, reversible inhibition of neurons the role of the PPTg in sensorimotor gating, measured as prepulse inhibition (PPI) of the acoustic startle response (ASR) using variable interstimulus intervals (ISI). In a second set of experiments we examined by the same technique the role of the PPTg in a progressive-ratio instrumental response task. METHODS: Local infusions of the GABA(A)-receptor agonist muscimol (0.05 microg and 0.5 microg/0.3 microl, or vehicle) were applied through indwelling microinfusion cannulae into the PPTg of freely moving rats. ASR and PPI were measured using acoustic stimuli of 100 dB (pulse) and 80 dB (prepulse) using ISIs of 25, 120, 520 and 1,020 ms. Instrumental behavior (lever pressing for casein pellets) was assessed in a Skinner box. Motor activity was measured in an open field. RESULTS: Intra-PPTg infusions of muscimol dose-dependently attenuated PPI at ISIs of 120 ms and 520 ms, but not at longer or shorter ISIs. ASR magnitude in pulse-alone trials was not significantly affected. Intra-PPTg infusion of 0.5 microg muscimol reduced the break point of instrumental responding (testing sequence where the rats fail to respond according to an increased ratio of reinforcement). No effects on food-preference and open-field activity were found. CONCLUSIONS: These findings suggest that GABAergic neurotransmission in the PPTg plays an important role for sensorimotor gating at intermediate ISIs and for response selection under demanding schedules of reinforcement.

Acetylcholinesterase↗
PubMed2002

The behavioral and dendritic growth effects of focal sensorimotor cortical damage depend on the method of lesion induction.

Using different models of focal cortical injury in adult rats, the neural structural and behavioral outcomes of unilateral lesions of the forelimb representation of the sensorimotor cortex (SMC) were assessed. Lesions were produced using either electrolytic, aspiration, or combined ('electroaspiration') techniques. Measurements of dendritic arborization in layer V of the motor cortex opposite the lesion revealed a growth of pyramidal neuron dendritic processes following electrolytic lesions in comparison to shams. This effect was not found in either the aspiration or electroaspiration lesion groups. Behaviorally, animals in all lesion groups developed a hyper-reliance on the forelimb ipsilateral to the lesion and proportionate disuse of the contralateral (impaired) forelimb for postural support behaviors. In comparison to sham-operated animals, the initial asymmetries in behaviors expressed during movement were similar between lesion groups, but were less enduring following electrolytic lesions than following aspiration and electroaspiration lesions. Furthermore, both aspiration lesion groups had more prevalent adduction of the impaired forelimb than the electrolytic-only lesion rats. Thus, cortical aspiration resulted in more severe and enduring forelimb impairments than the electrolytic lesions, despite similar lesion sizes, as assessed using cortical volume measures. These findings suggest that the aspiration lesion procedures, at least as performed in the present study, exacerbate the behavioral effects of focal cortical injury and limit compensatory plasticity in the contralateral cortex.

Animals↗
PubMed2004

Unilateral ischemic sensorimotor cortical damage in female rats: forelimb behavioral effects and dendritic structural plasticity in the contralateral homotopic cortex.

Previous studies in male rats with unilateral sensorimotor cortical (SMC) damage have demonstrated dendritic structural plasticity in the contralateral homotopic cortex and an enhancement of skilled reaching performance in the forelimb ipsilateral to the lesion compared to sham-operated rats. The purpose of this study was to determine if these findings could be replicated in an ischemic lesion model in female rats. Female rats were given sham operations or unilateral ischemic (endothelin-1 induced) damage in the forelimb representation area of the SMC opposite their preferred forelimb. Animals then received either 20 consecutive days of training on a skilled reaching task with the non-preferred/unimpaired forelimb or no-training control procedures. The surface density of dendrites immunoreactive (IR) for microtubule-associated protein 2 (MAP2) was then measured in the motor cortex opposite the trained limb and/or lesion. Female rats with sufficiently large, but not very small, lesions performed better with the unimpaired forelimb than sham-operated rats on the reaching task. The post-lesion reaching performance was not found to be significantly dependent upon estrous stage at the time of surgery, in agreement with previous studies that failed to find sex or sex-hormone effects after other types of SMC damage. Additionally, there were major laminar-dependent increases in the surface density of MAP2 IR dendrites in the cortex opposite lesions and trained limbs. These findings in female rats are consistent with the dendritic and behavioral changes previously found in male rats. They extend these previous findings by indicating that lesion size is an important variable in the enhancement of reaching performance.

Animals↗
PubMed1993

Modal gating of Na+ channels as a mechanism of persistent Na+ current in pyramidal neurons from rat and cat sensorimotor cortex.

The kinetic behavior of brain Na+ channels was studied in pyramidal cells from rat and cat sensorimotor cortex using either the thin slice preparation or acutely isolated neurons. Single-channel recordings were obtained in the cell-attached and inside-out configuration of the patch-clamp technique. Na+ channels had a conductance of about 16 pS. Patches always contained several Na+ channels, usually 4-12. In both preparations, long depolarizing pulses revealed two distinct patterns of late Na+ channel activity following transient openings. (1) Na+ channels displayed sporadic brief late openings sometimes clustered to "minibursts" of 10-40 msec. These events occurred at a low frequency, yielding open probability (NPo) values below 0.01 (mean = 0.0034). (2) In the second gating mode, an individual Na+ channel in the patch failed to inactivate and produced a burst of openings often lasting to the end of the pulse. This behavior was observed in about 1% of depolarizations. Shifts to the bursting mode were usually confined to a single 400 msec pulse, but rarely occurred during two or more consecutive pulses applied at 2 sec intervals. Sustained bursts did not require preceding transient openings to occur since they were also observed during slow depolarizing voltage ramps. The similar incidence of inactivation failures in cell-attached versus inside-out recordings suggests that the bursting mode is a property of the channel and/or adjacent membrane-bound structures. Calculations indicate that brief late openings and rare sustained bursts suffice to generate a small but significant whole-cell current. Since the Na+ channels mediating early, brief late, and sustained openings were identical in terms of their elementary electrical properties, we propose that the fast and the persistent Na+ currents of cortical pyramidal cells are generated by an electrophysiologically uniform population of Na+ channels that can individually switch between different gating modes.

Animals↗
PubMed2004

Auditory responses in multiple sensorimotor song system nuclei are co-modulated by behavioral state.

Auditory responsiveness in nucleus HVC, a high-order sensorimotor area of the avian song system, is modulated by changes in behavioral state. Modulation is not observed in the primary thalamo-recipient auditory area Field L, the indirect source of auditory input to HVC. In this study, we show that auditory responsiveness in nucleus interfacialis (NIf), the immediate auditory afferent to HVC, is modulated by behavioral state. While auditory responsiveness is generally greater in NIf during wakefulness and in HVC during sedation, simultaneous recordings reveal a co-variation of auditory response magnitude. This co-variation is observed both in awake birds, where responses are spontaneously variable, and in sedated birds during manipulations of arousal levels. Auditory responses in NIf and HVC, which are selective for the bird's own song (BOS) during sedation, become predominantly unselective during wakefulness. This loss of selectivity is accompanied by a decrease in the similarity of NIf and HVC response patterns. To explore the role of NIf in shaping HVC auditory responses, we pharmacologically manipulated NIf while recording in HVC. Injection of the GABA(A) agonist muscimol into NIf eliminated most spontaneous activity and all auditory responses in the ipsilateral HVC, while injections of the GABA(A) antagonist bicuculline increased HVC auditory responsiveness and selectivity. These findings indicate that HVC is not the initial site of behavioral state-dependent modulation in the song system. Together with the suppression of HVC auditory responses by muscimol in NIf, these results suggest that NIf plays an important role in the flow of auditory information to HVC.

Acoustic Stimulation↗
PubMed2001

Prepulse inhibition deficits and perseverative motor patterns in dopamine transporter knock-out mice: differential effects of D1 and D2 receptor antagonists.

Dopamine is known to regulate several behavioral phenomena, including sensorimotor gating and aspects of motor activity. The roles of dopamine D1 and D2 receptors in these behaviors have been documented in the rat literature, but few reports exist on their role in mice. We used dopamine transporter (DAT) (-/-) mice to examine the behavioral consequences of a chronically hyperdopaminergic state, challenging them with the preferential dopamine D2 receptor antagonist raclopride and D1 receptor antagonist SCH23390. At baseline, DAT (-/-) mice exhibited deficient sensorimotor gating as measured by prepulse inhibition (PPI) of the startle response, exhibited nonfocal preservative patterns of locomotion, and were hyperactive in a novel environment. Pretreatment with raclopride significantly increased PPI in the DAT (-/-) mice, whereas SCH23390 had no significant effect. Blockade of D2 receptors did not affect the predominantly straight patterns of motor behavior produced by the DAT (-/-) mice, but antagonism of D1 receptors significantly attenuated the preservative patterns, producing more of a meandering behavior seen in the DAT (+/+) control mice. Both D1 and D2 receptor antagonists decreased the hyperactivity seen in the DAT (-/-) mice. These findings support the role of the D2, but not the D1, receptor in the modulation of PPI in mice. Furthermore, D1 receptor activation appears to be the critical substrate for the expression of preservative patterns of motor behavior, whereas both D1 and D2 receptors appear to regulate the amount of motor activity.

Animals↗
PubMed2001

Prenatal exposure to anti-HIV drugs: neurobehavioral effects of zidovudine (AZT) + lamivudine (3TC) treatment in mice.

BACKGROUND: The new antiretroviral treatments that combine the zidovudine (AZT) regimen with lamivudine (3TC) appear as a cost-effective alternative to the current AZT monotherapy to prevent mother-to-fetus transmission of the HIV-1 virus. Recent evidence in uninfected children raised concern about the long-term effects of perinatal exposure to AZT and 3TC, especially when used in combination. Animal studies indicated behavioral changes in offspring exposed perinatally to both AZT and 3TC, whereas no animal data are available on the effects of the perinatal exposure to the AZT + 3TC combination on neurodevelopment. METHODS: Pregnant CD-1 mice received p.o. AZT + 3TC (160 and 500 mg/kg, respectively) or vehicle solution (NaCl 0.9%) twice daily from gestational day 10 to delivery. Maternal reproductive endpoints such as pregnancy length, abortion, litter size, sex ratio, and offspring viability were assessed. Pups were scored for different somatic and behavioral endpoints, including sensorimotor development, homing performance on postnatal day (PND) 10, passive-avoidance testing (PND 22-23), locomotor activity (PND 23), and social interaction (PND 35). RESULTS: While no effects were observed on maternal reproductive endpoints, treated pups showed a long-lasting reduction of body weight and a slightly delayed maturation of placing and grasping reflexes and pole grasping. No effects on passive-avoidance or locomotor activity were found. AZT + 3TC-treated mice showed selective alterations in the social interaction test; the treated female offspring also displayed a significant reduction of affiliative interactions. CONCLUSIONS: The combination of AZT and 3TC (1) induced small, but more marked, effects on somatic and sensorimotor development than either of these drugs administered separately; and (2) affected juvenile social behavior.

Animals↗
PubMed2002

The window of opportunity for administration of magnesium therapy following focal brain injury is 24 h but is task dependent in the rat.

The present study was conducted to establish the window of opportunity for the administration of a regimen of MgCl2 pharmacotherapy following focal injury to the brain. Rats were subjected to unilateral electrolytic lesions of the sensorimotor cortex (SMC) and administered a regimen of MgCl2 (1.0 mmol/kg) or 0.9% saline (1.0 ml/kg) beginning either 15 min, 8 h or 24 h after injury. Subsequent injections were administered 24 and 72 h after the initial treatment. Behavioral testing assessed recovery of function on several sensorimotor behaviors for 24 days following injury. The results of the present study suggest that treatment with a regimen of MgCl2 significantly facilitated recovery of function on the forelimb-->forelimb and vibrissae-->forelimb placing tests when administered 15 min, 8 h or 24 h after injury compared with saline-treated rats. Recovery of locomotor placing was significantly facilitated at 15 min and 8 h but not at 24 h compared with saline-treated rats. In addition, the ability of MgCl2 to limit neuronal loss in the ipsilateral ventral posterior lateral (VPL) nucleus of the thalamus was seen at only the 15-min treatment interval. These results suggest that the window of opportunity for MgCl2 pharmacotherapy is 24 h, task dependent and is much shorter for protecting neurons in the VPL.

Animals↗
PubMed1987

Cholinergic receptor blockade produces impairments in a sensorimotor subsystem for place navigation in the rat: evidence from sensory, motor, and acquisition tests in a swimming pool.

Studies have shown that central cholinergic receptor blockade biases the behavior of rats so that they make less use of the sensorimotor behaviors that are normally used to orient to the relational properties of distal cues and that they simultaneously become more reliant on proximal cues. In Experiment 1, control rats and rats treated with atropine sulfate or atropine methyl nitrate (50 mg/kg) were trained to escape to a visible platform from different starting points in a swimming pool. All groups learned the task by concomitantly developing position responses, by orienting according to room cues, and by orienting to the platform, but probe trials showed that the atropine-sulfate group made more use of the platform as a local cue and made less use of distal cues than did the other groups. The atropine-sulfate group also made fewer searches during acquisition, made fewer searches when the platform was removed on probe trials, and were less responsive to novel cues placed above and around the pool. Swim speed, as estimated by the distance swum on probe trials, was also greater in atropine-sulfate-treated rats. The postulate that rats treated with atropine sulfate preferentially guide swimming by using position responses and local cues was tested in Experiment 2 by comparing their performance with that of control rats in a place task in which a target platform was hidden (no local cues present) and in a similar place task in which the target platform was visible, as was a second incorrect platform that sank when climbed upon (two competing local cues present). Although both tasks were acquired by the control and drugged rats, the two-platform task, as predicted, was comparatively more difficult for the atropine-treated rats. These results suggest that one effect of central cholinergic blockade is to impair the use of a sensorimotor subsystem used for place navigation.

Animals↗
PubMed1996

Detailed behavioral analysis of water maze acquisition under systemic NMDA or muscarinic antagonism: nonspatial pretraining eliminates spatial learning deficits.

A detailed behavioral analysis of water-maze acquisition showed that the N-methyl-D-aspartate (NMDA) antagonist NPC17742 and the muscarinic antagonist scopolamine caused sensorimotor disturbances in behaviors required for maze performances and that these correlated with acquisition impairments in both hidden and visible platform versions of the maze in male rats. Behavioral disturbances included thigmotaxic swimming, swimming over and deflecting off the platform, abnormal swim behavior, and hyperactivity. Rats familiar with the behavioral strategies involved in the task performed normally under NPC17742 or scopolamine. The results indicated that drug-induced sensorimotor disturbances contributed to poor acquisition scores in naive rats. NMDA or muscarinic activity may contribute to but do not appear to be essential for spatial learning in the water maze.

Amino Acids↗
PubMed1996

Oscillatory activity in sensorimotor cortex of awake monkeys: synchronization of local field potentials and relation to behavior.

1. Oscillations of 20-40 Hz were observed in local field potentials (LFPs) and unit activity in sensorimotor cortices of three awake monkeys while the monkeys performed trained wrist movements and untrained exploratory arm movements. The mean frequency of LFP oscillations was 25.9 +/- 1.4 (SD) Hz and the number of cycles of oscillations per episode was variable, with a mean of 4.2 +/- 0.5 (mean +/- SE). 2. Oscillatory episodes occurred most often when the monkeys retrieved raisins from a Klüver board (0.59 +/- 0.23 episodes per s, mean +/- SD) or from unseen locations with the use of somatosensory feedback (0.62 +/- 0.12 episodes per s); they occurred less often when the monkeys performed repetitive wrist flexion and extension movements (0.22 +/- 0.04 episodes per s) or sat quietly at rest (0.23 +/- 0.17 episodes per s). 3. The amplitude of LFP oscillations increased with depth in cortex, reaching a maximum between 1 and 2 mm. LFP oscillations at the surface of the cortex were 180 degrees out of phase with oscillations in the deep cortical layers. The phase shift (with respect to the deep layers) decreased with depth in the cortex and disappeared at depths of > 1 mm. 4. LFPs were recorded simultaneously at multiple sites in the sensorimotor cortex when monkeys retrieved raisins from a Klüver board or from unseen locations. Cross-correlation of LFPs recorded at different sites indicated that oscillations in the 20- to 40-Hz range could become synchronized at sites separated by up to > or = 14 mm in the precentral cortex. 5. The probability of occurrence of significant correlations between LFP oscillations at paired sites and the average correlation amplitude decreased with increasing horizontal separation of sites in precentral cortex. The phase shift between LFP oscillations recorded at paired sites did not change significantly with increasing horizontal separation. 6. For paired sites in precentral cortex, the average strength of correlations and the proportion of oscillations that were significantly correlated were greater during exploratory behaviors such as retrieving raisins from slots of the Klüver board than during periods of rest or overtrained wrist movements. 7. Oscillations could become synchronized with small phase shifts (0.5 +/- 1.6 ms) between pre- and postcentral cortical sites. Average strength and probability of occurrence of significant correlations between pre- and postcentral LFPs increased during exploratory behaviors. 8. Oscillations occurred simultaneously in the left and right motor cortex and could become synchronized with negligible phase shifts when the monkey performed bimanual manipulations. However, synchronization occurred as often and as strongly for unimanual as for bimanual manipulations. 9. These results indicate that episodes of 20- to 40-Hz oscillations occur often and become synchronized over a large cortical area during exploratory forelimb movements. However, they have no reliable relation to particular components of the movement and therefore seem unlikely to be involved directly in movement execution; instead, they may represent a neural correlate of attention during demanding sensorimotor behaviors.

Animals↗
PubMed2005

Representation of immediate and final behavioral goals in the monkey prefrontal cortex during an instructed delay period.

We examined neuronal activity in the lateral prefrontal cortex of monkeys performing a path-planning task in a maze that required the planning of actions in multiple steps. The animals received an instruction that prompted them to prepare to move a cursor in the maze stepwise from a starting position to a goal position by operating manipulanda with either arm. During a delay period in which the animal prepared to start the first of three cursor movements to approach the pre-instructed goal, we identified two types of neuronal activity: the first type reflected the position within the maze to which the animal intended to move the cursor as an initial step (an immediate goal) and the second type reflected the position within the maze that was to be captured as a final goal. Neither type reflected motor responses. We propose that these two types of neuronal activity are neuronal correlates that represent immediate and ultimate behavioral goals. This finding implicates the prefrontal cortex in governing goal-oriented sequential behavior rather than sensorimotor transformation.

Algorithms↗
PubMed1996

Traumatic brain injury of the forelimb and hindlimb sensorimotor areas in the rat: physiological, histological and behavioral correlates.

This study characterizes physiological, histological and behavioral effects of traumatic brain injury (TBI) produced by a controlled pneumatic impactor striking the entire right sensorimotor cortex of the anesthetized rat. Damage to both the fore- and hindlimb sensorimotor areas resulted in a hemiparetic animal which allowed us to use four sensitive behavioral/neurological tests to track the recovery sequelae after injury. Initial experiments measured cardiovascular and respiratory effects after cortical impact which depressed the dura to varying depths. Both 0.5 mm and 1 mm cortical depressions produced a momentary decrease (P < 0.05) in mean arterial blood pressure (MABP) while cortical impacts to depths of 2 mm or 3 mm produced a momentary increase (P < 0.05) in MABP. Normotension was re-established within 30 s after the initial response at all injury levels. Respiratory rate was affected only following 3 mm cortical depressions. A 1 mm cortical depression appeared ideal in terms of minimal cardiorespiratory effects, low mortality and lasting behavioral effects. For behavioral and histologic studies, therefore, additional rats were injured by a 1 mm cortical impact and tested for 8 weeks after TBI using four behavioral tests. Injured rats displayed both fore- and hindlimb deficits up to 56 days while traversing a narrow beam (P < 0.001) and up to 28 days when crossing a pegged beam (P < 0.05). Forelimb deficits evaluated on a wire grid platform were evident for 28 days (P < 0.05). Forepaw preference measured in a non-test setting indicated a bias to use the unaffected forepaw for 35 days (P < 0.05). A biphasic pattern of functional recovery was seen on all tests. A period of rapid functional recovery lasting 7 to 10 days was followed by a slower period of functional recovery lasting many weeks. Possible meanings of this biphasic recovery are discussed as issues of behavioral compensation/adaptation versus true neural recovery. Eight weeks after TBI histological analyses indicated that axonal degeneration was present in the areas adjacent to the ipsilateral cortical injury site. Degenerating fibers also extended across the corpus callosum into the homologous area in the contralateral cortex and were seen in the ipsilateral striatum, somatosensory and motor thalamic nuclei and substantia nigra. Significant axonal degeneration occurred bilaterally around the deep cerebellar nuclei. Degenerating fibers extended into the folia and terminated in the cerebellar granule cell layer. Thus the entire sensorimotor control system appeared to have been affected by a cortical injury.

Animals↗
PubMedDate not supplied

Behavioral and neurochemical sequelae in young rats of antenal hypoxia.

To test the hypothesis that perinatal hypoxia may have postnatal consequences via à vis learning memory, and neurochemical sequelae, we exposed pregnant Sprague-Dawley rats to 10.5% O2 for 4 h per day (0800-1200 h) or continuously from gestional day E15 to E20. On E20 we quantified ornithine decarboxylase activity and polyamine concentrations in fetal brain. We also conducted behavioral tests from postnatal day P3 to P110. Relatively mild antenatal hypoxia resulted in altered learning, memory, and delayed maturation of early developmental sensorimotor function. These behavioral changes disappeared at various postnatal ages, depending on the function. Perinatal hypoxia also altered the pharmacological response to dopaminergic drugs. In addition, antenatal hypoxia feminized a male nonreproductive sexual behavior, that of saccharin preference. Acute hypoxia also resulted in an increase in the enzyme ornithine decarboxylase and polyamines, which may affect brain development.

Animals↗
PubMed2004

Behavioral and neuroplastic effects of focal endothelin-1 induced sensorimotor cortex lesions.

Previous studies have established the usefulness of endothelin-1 (ET-1) for the production of focal cerebral ischemia. The present study assessed the behavioral effects of focal ET-1-induced lesions of the sensorimotor cortex (SMC) in adult rats as well as cellular and structural changes in the contralateral homotopic motor cortex at early (2 days) and later (14 days) post-lesion time points. ET-1 lesions resulted in somatosensory and postural-motor impairments in the contralateral (to the lesion) forelimb as assessed on a battery of sensitive measures of sensorimotor function. The lesions also resulted in the development of a hyper-reliance on the ipsilateral forelimb for postural-support behaviors. In comparison to sham-operated rats, in layer V of the motor cortex opposite the lesions, there were time- and laminar-dependent increases in the surface density of dendritic processes immunoreactive for microtubule-associated protein 2, in the optical density of N-methyl-D-asparate receptor (NMDA) subunit 1 immunoreactivity, and in the numerical density of cells immunolabeled for Fos, the protein product of the immediate early gene c-fos. These findings corroborate and extend previous findings of the effects of electrolytic lesions of the SMC. It is likely that compensatory forelimb behavioral changes and transcallosal degeneration play important roles in these changes in the cortex opposite the lesion, similar to previously reported effects of electrolytic SMC lesions.

Animals↗