Differential effects of chronic spinal hemisection on somatic and visceral inputs to caudal brainstem

The medullary reticular formation (MRF) receives convergent inputs from multiple somatic and pelvic/visceral territories. The effects of chronic 30-day lateral hemisections at T8 on the responses of single MRF neurons to noxious mechanical stimulation of both hindpaws was examined in urethane-anesthetized male rats. Neuronal responses on both sides of the MRF to pinching of the hindpaw on the side opposite the lesion (intact-side) were found either to be completely absent or if present, weak (i.e. hindpaw was hyposensitive). The presence or absence of intact-side responses appeared to be dependent on the lesion extent. In contrast, bilateral MRF responses to pinching the lesion-side hindpaw were present; however, responses were greater in magnitude (lower thresholds) relative to surgical sham controls suggesting hypersensitivity. Responses to lesion-side hindpaw stimulation on both sides of the MRF indicated that whereas the ascending projections are primarily crossed below the level of lesion, they are both crossed and uncrossed above. These findings are in contrast with our previous data on ascending projections from the bilaterally organized male urogenital tract. The results presented for the hindpaws correlate with clinical observations of patients with similar incomplete spinal cord injuries (Brown-Séquard syndrome).     

Sympathetic sprouting reverses decreases in membrane-associated activity of protein kinase C following septohippocampal denervation of the rat hippocampus

Hippocampal sympathetic ingrowth (HSI), a form of neuronal plasticity, is induced by medial septal lesions and consists of the sprouting of peripheral sympathetic fibers, arising from the superior cervical ganglion, into the dentate gyrus and CA₃ region of the hippocampus. HSI has been previously shown to alter learned and spontaneous behaviors, phosphatidyl inositide hydrolysis, and the antagonist binding kinetics of both muscarinic cholinergic receptors and phorbol ester receptors. We now report that sympathetic sprouting reverses decreases in membrane-associated activity of protein kinase C (PKC) following septohippocampal denervation of the rat hippocampus. Further, no changes were found in α, β or γ PKC isoenzymes among experimental groups, suggesting that the group A PKC isoforms do not mediate the observed changes in activity and phorbol ester binding.     

Co-activation of glutamate and dopamine receptors within the nucleus accumbens is required for spatial memory consolidation in mice

Rationale The nucleus accumbens receives glutamatergic and dopaminergic inputs converging onto common dendrites. Recent behavioral data demonstrated that intra-accumbens administrations of either glutamate or dopamine (DA) antagonist impair spatial memory consolidation. Thus, also based on the biochemical and molecular findings demonstrating interactions among the different receptors subtypes for glutamate and dopamine, it is conceivable that memory consolidation within this structure might be modulated by glutamate–dopamine receptor interactions.Objectives The purpose of this study was to examine the effects of intra-accumbens co-administrations of glutamate and DA antagonists on the consolidation of spatial information.Methods On day 1, CD1 male mice were placed in an open field containing five different objects and immediately after three sessions of habituation the animals were injected intra-accumbens with either vehicle or low doses of the N-methyl-d-aspartate (NMDA; AP-5 50 ng/side), the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA; DNQX 5 ng/side), the D1 (SCH23390 12.5 ng/side) and the D2 (sulpiride 25 ng/side) antagonists that were ineffective alone in disrupting object displacement. Separate groups were then focally injected with a combination of one of the glutamate antagonists with one of the dopamine antagonists. Twenty-four hours later, the ability of mice to discriminate object displacement was assessed.Results Controls and mice injected with ineffective doses of the NMDA, the AMPA, the D1 or the D2 antagonists were always able to react to the object displacement. On the contrary, the groups administered with the different combinations (AP-5 and SCH23390, AP-5 and sulpiride, DNQX and SCH23390, DNQX and sulpiride) of glutamate and dopamine antagonists did not discriminate the spatial change.Conclusions These results demonstrate that glutamate–dopamine receptor interactions within the accumbens are essential for the consolidation process of spatial information.     

Hand somatosensory cortex activity following selective dorsal rhizotomy: report of three cases with fMRI

Introduction Selective dorsal rhizotomy (SDR) is an effective treatment for lower extremity spasticity in cerebral palsy. Cortical organization in sensory cortex may be abnormal in cerebral palsy, and deafferentation is known to lead to cortical reorganization in many situations.Methods We used functional magnetic resonance imaging (fMRI) of hand sensory stimulation to determine if the partial deafferentation of the lower extremity sensory system, associated with SDR, led to any alterations in the cortical somatosensory representation for the upper limbs. Three patients with spastic diplegia were studied with blood oxygen level-dependent (BOLD)-fMRI before and after SDR. fMRI during tactile stimulation of the digits of the right hand was used to map hand somatosensory cortex. Comparison of the cortical maps devoted to the hand before and after SDR assessed for cortical reorganization following partial deafferentation of the lower extremity.Results In the one patient with upper extremity involvement, the hand sensory representation was markedly enhanced following SDR. In the other two patients, a normal pattern, but with diminished activity, was seen compared with preoperative findings. SDR for lower limb spastic diplegia does not lead to extensive reorganization of cortex dedicated to the representation of the upper limb. An essentially normal pattern of activation was seen both before and after SDR.Conclusion The relief of attention demands associated with spasticity may explain the modulation in intensity seen after SDR in the patients who exhibited no upper extremity involvement despite lower limb spasticity.     

Differences in forebrain activation in two strains of rat at rest and after spinal cord injury

Forebrain activation patterns in normal and spinal-injured Sprague-Dawley (SD) rats were determined by measuring regional cerebral blood flow as an indicator of neuronal activity. Data are compared to our previously published findings from normal and spinal-injured Long-Evans (LE) rats and reveal a striking degree of overlap, as well as differences, between strains in the basal (unstimulated) forebrain activation in normal animals. Specifically, 81% of the structures sampled showed similar activation in both strains, suggesting a consistent and identifiable pattern of basal cerebral activation in the rat. LE controls showed significantly greater basal activation in the remaining structures compared to SD control group, including the anterior dorsal thalamus, basolateral amygdala, SII cortex, and the hypothalamic paraventricular nucleus. In contrast, spinal cord injury (SCI) resulted in strain-specific changes in forebrain activation categorized by structures that showed significant increases in: (1) only LE SCI rats (posterior, ventrolateral, and ventroposterolateral thalamic nuclei); (2) only SD SCI rats (anterior-dorsal and medial thalamus, basolateral amygdala, cingulate and retrosplenial cortex, habenula, interpeduncular nucleus, hypothalamic paraventricular nucleus, periaqueductal gray); or (3) both strains (arcuate nucleus, ventroposteromedial thalamus, SI and SII somatosensory cortex). These results provide information related to the remote, i.e. supraspinal, effects of spinal cord injury and suggest that genetic differences play an important part in the forebrain response to such injury. Brain activation studies therefore provide a useful tool in understanding the full extent of secondary consequences following spinal injury and for identifying potential central mechanism responsible for the development of pain.     

Tactile functions after cerebral hemispherectomy

Patients that were hemispherectomized due to brain lesions early in life sometimes have remarkably well-preserved tactile functions on their paretic body half. This has been attributed to developmental neuroplasticity. However, the tactile examinations generally have been fairly crude, and subtle deficits may not have been revealed. We investigated monofilament detection and three types of tactile directional sensibility in four hemispherectomized patients and six healthy controls. Patients were examined bilaterally on the face, forearm and lower leg. Normal subjects were examined unilaterally. Following each test of directional sensibility, subjects were asked to rate the intensity of the stimulation. On the nonparetic side, results were almost always in the normal range. On the paretic side, the patients' capacity for monofilament detection was less impaired than their directional sensibility. Despite the disturbed directional sensibility on their paretic side the patients rated tactile sensations evoked by the stimuli, on both their paretic and nonparetic body halves, as more intense than normals. Thus, mechanisms of plasticity seem adequate for tactile detection and intensity coding but not for more complex tactile functions such as directional sensibility. The reason for the high vulnerability of tactile directional sensibility may be that it depends on spatially and temporally precise afferent information processed in a distributed cortical network.     

Protein synthesis is necessary for dendritic spine proliferation in adult brain slices

Dendritic spines, small protrusions from dendritic shafts, receive most of the excitatory synapses in cortical regions. Spines are highly plastic structures that can be rapidly produced or lost in response to a wide array of internal and external stimuli, and they proliferate in acute slice preparations [J. Neurosci. 19 (1999) 2876]. The goal of the present study was to determine if protein synthesis is necessary for this spine proliferation. We found that the addition of protein synthesis inhibitors to acute slices (in which spines otherwise proliferate) blocked new spine growth. Furthermore, a population of longer spines was observed after 2 h but these did not develop during protein synthesis blockade. These data suggest that protein synthesis is necessary for new spine growth in acute brain slice preparations and support literature suggesting that newly produced spines develop from filopodia-like protrusions.     

Short-term, D2 receptor blockade induces synaptic degeneration, reduces levels of tyrosine hydroxylase and brain-derived neurotrophic factor, and enhances D2-mediated firing in the ventral pallidum

Repeated treatments with neuroleptics are associated with biochemical and morphological alterations in forebrain neurons as well as an upregulation of D2-mediated changes in neuronal function. The present study evaluated the histological and physiological effects of three once-daily treatments with two chemically divergent neuroleptics, haloperidol (1 mg/kg i.p./day) and eticlopride (3 mg/kg i.p./day), measured in rats 24 h after the last injection. It was determined that this short-term antagonism of D2-like receptors induced fiber and terminal degeneration and significantly decreased tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF) immunoreactivity in the ventral pallidum (VP), as determined by optical density measurements. While other forebrain regions demonstrated changes in TH and BDNF, the neurodegeneration profile was unique to the VP. This was accompanied by an enhancement in the efficacy of the D2 agonist quinpirole to increase spiking rate of VP neurons recorded in chloral hydrate-anesthetized rats. These data indicate that short-term treatments with D2 antagonists are sufficient to induce changes in the biochemical and morphological profiles uniquely within the VP. Moreover, the functional ramifications of these changes appear to include profound alterations in the way dopamine regulates neuronal activity in this region.     

Age-dependent effects of nicotine on locomotor activity and conditioned place preference in rats

Rationale Most adult smokers start smoking during their adolescence. This adolescent initiation may be due to multiple factors, but little evidence is available regarding whether their brains are differentially sensitive to the addictive effects of nicotine during adolescence.Objective To test the hypothesis that adolescents are more sensitive than adults to nicotines rewarding actions.Methods An unbiased, counterbalanced, place-conditioning procedure was used to examine drug-induced reward and locomotor activity. Early adolescent (postnatal day 28), late adolescent (P38) and adult (P90) rats received either saline or nicotine (0.125, 0.25 or 0.5 mg/kg, s.c.) and were tested for place conditioning.Results During early adolescence, a single nicotine injection (0.5 mg/kg) induced significant conditioned place preference (CPP). In contrast, during late adolescence or adulthood, nicotine did not induce CPP after either one or four conditioning trials. Initial locomotor responses to acute nicotine administration during the first conditioning trial also differed with age, with no effect at P28, but substantial inhibitory responses at all doses studied (0.125–0.5 mg/kg) at later ages. Although not differing in their initial locomotor response to nicotine, there was a significantly greater tolerance/sensitization during the second and subsequent drug exposures in late adolescents than in adults.Conclusions These findings provide evidence that adolescent brain is differentially sensitive to both the acute and repeated effects of nicotine relative to adult brain. Furthermore, there are significant differences in nicotine sensitivity between early and late phases of adolescence.     

Considerations for use of the Hoffmann reflex in exercise studies

There continues to be great interest in evaluating the adaptive plasticity of the human nervous system in response to exercise training or other interventions. For various reasons, researchers have been interested in estimates of spinal reflex processing in intact human subjects before and after training. A reflex pathway that has been employed in this regard is the Hoffmann (H) reflex. This brief review describes the basic procedure for evoking the H reflex in different muscles. Other sections address methodological issues that affect interpretation of the H reflex. In particular, the role that presynaptic inhibition serves in the modification of the H reflex and how this precludes its use as an unambiguous measure of alpha-motoneuron excitability will be discussed. Applications of the H reflex to study adaptive plasticity in humans is also reviewed, and methodological requirements that should be maintained for accurate interpretation of H reflexes in exercise studies are presented. Electronic Publication