bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrinsic optical signals in the dorsal horn of rat spinal cord slices elicited by brief repetitive stimulation
Authors: Asai Tatsuya , Kusudo Kei , Ikeda Hiroshi , Murase Kazuyuki 
Published: March 2003

AbstractWith repetitive electrical stimulation of the dorsal root (20 Hz for 1 s at C‐fibre strength), intrinsic optical signals (IOSs), measured as changes in light transmittance, were recorded in the superficial dorsal horn of rat spinal cord slices using a photodiode array imaging device. The mechanism underlying the induction of IOSs was investigated. IOSs elicited by brief repetitive stimulation persisted for 1–2 min and were decreased by reducing external Cl– concentration or by cation–chloride cotransport inhibitors. Furosemide was most effective whilst bumetanide was least effective among the inhibitors tested. A 1‐min elevation of external K+ concentration evoked IOSs in the dorsal horn in the absence of stimulation, and K+‐induced IOSs were inhibited by furosemide. These results suggest that the uptake of excess K+ via the furosemide‐sensitive, cation–chloride cotransporters underlies the induction of the IOSs. One‐minute exposure to hypotonic solutions, which would cause cell swelling, induced IOSs in the superficial dorsal horn. Whilst osmotic‐induced IOSs were not affected by furosemide, they were inhibited by HgCl2 in a 2‐mercaptoethanol‐sensitive manner. The stimulation‐induced IOSs were similarly depressed by HgCl2. In contrast, voltage‐sensitive dye signals and field potentials, evoked by single electrical stimuli, were significantly less affected by HgCl2. These results suggest that there is a specialized water transport pathway in the superficial dorsal horn, and that IOSs elicited by brief repetitive activation of C‐fibres are attributable to cell swelling caused by water influx through this pathway, as an osmotic gradient is established by the uptake of K+ via the furosemide‐sensitive cotransporters.
Expression of fractalkine and its receptor, CX3CR1, in response to ischaemia‐reperfusion brain injury in the rat
Authors: Tarozzo Glauco , Campanella Marilena , Ghiani Michela , Bulfone Alessandro , Beltramo Massimiliano 
Published: March 2003

AbstractFractalkine is a neuronally expressed chemokine that acts through its G‐protein‐coupled receptor CX3CR1, localized on microglial and immune cells. Fractalkine might be involved in neuroinflammatory processes secondary to neuronal damage, which normally occur in a time frame of days after ischaemia. We evaluated by in situ hybridization and immunohistochemistry the expression of fractalkine and CX3CR1 in the rat brain, after a transient occlusion of the middle cerebral artery. We found that at 12 h after ischaemia neuronal fractalkine expression was transiently increased in scattered necrotic neurons of the cortex and lost from the ischaemic striatum. At 24 and 48 h after ischaemia, fractalkine immunoreactivity was strongly increased in morphologically intact cortical neurons of the ischaemic penumbra where also the stress‐inducible HSP‐72 was strongly up‐regulated. The intensity of fractalkine immunoreactivity of neurons in the penumbra returned to basal levels at 7 days after ischaemia. Fractalkine synthesis was also induced in endothelial cells of the infarcted area, at 48 h and 7 days after ischaemia. CX3CR1 expression was detected in the activated microglial cells of the ischaemic tissue 24 and 48 h after ischaemia, and became strongly up‐regulated in macrophages/phagocytic microglia inside the infarcted tissue 7 days after ischaemia. These data suggest that fractalkine may participate in the activation and chemoattraction of microglia into the infarcted tissue, and contribute to the control of leucocyte trafficking from blood vessels into the injured area.
NMDA receptor‐mediated metaplasticity during the induction of long‐term depression by low‐frequency stimulation
Authors: Mockett Bruce , Coussens Christine , Abraham Wickliffe C. 
Published: March 2003

AbstractMetaplasticity refers to the activity‐dependent modification of the ability of synapses to undergo subsequent synaptic plasticity. Here, we have addressed the question of whether metaplasticity contributes to the induction of long‐term depression (LTD) by low‐frequency stimulation (LFS). The experiments were conducted using standard extracellular recording techniques in stratum radiatum of area CA1 in hippocampal slices made from adult Sprague–Dawley rats. The degree of LTD induction was found to be a nonlinear function of the number of pulses during a 1‐Hz LFS. Little LTD was observed following 600 or 900 pulses, but a significant LTD occurred following 1200 pulses of LFS, whether delivered in one episode, or in two bouts of 600 pulses given 10 min apart. A similar pattern was observed for 3 Hz LFS. The data support the suggestion that pulses occurring early in the LFS train prime synapses for LTD induction, as triggered by later occurring stimuli. The priming effect lasted at least 120 min, when tested by giving two bouts of 1 Hz LFS (600 pulses each) at different intervals. Neither heterosynaptic nor homosynaptic stimulation by itself was sufficient to prime LTD. However, a combination of the stimuli, induced by increased stimulus strength during the LFS, appeared necessary for inducing the effect. An N‐methyl‐d‐aspartate (NMDA) receptor antagonist markedly reduced total LTD induction, regardless of whether it was administered during the first or second LFS in a protocol employing two bouts of 600 pulse LFS, 30 min apart. These findings strongly support the hypothesis that NMDA receptor‐dependent metaplasticity processes contribute to the induction of LTD during standard LFS protocols.
The basolateral complex of the amygdala is necessary for acquisition but not expression of CS motivational value in appetitive Pavlovian second‐order conditioning
Authors: Setlow Barry , Gallagher Michela , Holland Peter C. 
Published: March 2003

AbstractThe basolateral complex of the amygdala (ABL) is involved in processing information about stimulus motivational value. However, it is not clear whether the ABL is critical for acquisition, maintenance, or expression of this information. Our previous work has shown that ABL lesions made prior to training, block acquisition of an appetitive Pavlovian second‐order conditioning task, in which performance is thought to depend on the acquisition of motivational (conditioned reinforcement) value by the first‐order conditioned stimulus (CS). The present experiments examined the effects of ABL lesions made after first‐order conditioning, when the CS acquires motivational value, but before second‐order conditioning, the test for acquired value of that CS. Rats received pairings of a visual CS with a food reinforcer. They then received bilateral sham or excitotoxic lesions of the ABL. After recovery, they received pairings of a second‐order auditory CS with the previously conditioned visual CS. In two experiments, both sham and lesioned rats acquired normal second‐order conditioned behaviours. Some of the same rats were then given another round of second‐order conditioning with novel CSs. In this case, when first‐order training occurred after surgery, some second‐order conditioned behaviours were impaired in lesioned rats. Tests of the associative underpinnings of second‐order conditioned behaviours showed that those behaviours impaired by ABL lesions were based on stimulus–response associations. The results show that although the ABL is critical for second‐order conditioning, this role is limited to acquisition of information about the motivational value of the first‐order CS, and it is not critical for maintenance of this information or for its use in forming second‐order associations.
The age‐related increase in IL‐1 type I receptor in rat hippocampus is coupled with an increase in caspase‐3 activation
Authors: Lynch Aileen M. , Lynch Marina A. 
Published: March 2003

AbstractEvidence from several studies indicates that expression of interleukin‐1β (IL‐1β) and IL‐1 type I receptor is particularly high in hippocampus, and it has recently been shown that the concentration of IL‐1β is increased in the hippocampus of the aged rat. Here we report that this increase is coupled with an increase in expression of IL‐1 type I receptor and increased activity of IL‐1 receptor‐associated kinase. The evidence presented indicates that the age‐related increase in activity of the mitogen‐activated protein kinases, Jun N‐terminal kinase (JNK) and p38, was accompanied by enhanced caspase‐3 activity. Analysis of colocalization of activated caspase‐3 with activated p38 (p‐p38) suggested that p‐p38 was necessary for activation of caspase‐3; while in vitro analysis indicated that the IL‐1β‐induced increase in caspase‐3 activity was abrogated by the p38 inhibitor, SB203580. The IL‐1β‐induced increase in caspase‐3 activity in vitro was also abrogated by vasoactive intestinal peptide, which is a JNK inhibitor; however, colocalization of activated JNK (p‐JNK) and activated caspase‐3 did not clearly identify JNK as an upstream activator of caspase‐3. We propose that these changes are indicative of cell death in aged hippocampus and suggest that they contribute to the age‐related decrease in long‐term potentiation in perforant path granule cell synapses.
Expression and dendritic mRNA localization of GABAC receptor ρ1 and ρ2 subunits in developing rat brain and spinal cord
Authors: Rozzo Aldo , Armellin Mara , Franzot Jessica , Chiaruttini Cristina , Nistri Andrea , Tongiorgi Enrico 
Published: March 2003

AbstractThe cellular distribution of GABAC receptor ρ1 and ρ2 subunits in the rat central nervous system remains controversial. We investigated how these subunits were distributed in cerebellum, hippocampus and spinal cord at postnatal day 1, 7 or in adult life. We found that in the adult cerebellum ρ1 and ρ2 mRNAs were expressed in Purkinje cells and basket‐like cells only. In the hippocampus both subunits were expressed throughout the CA1 pyramidal layer, dentate gyrus and scattered interneurons with maximum staining intensity at P7. In the adult hippocampus in situ staining was predominantly found on interneurons. GABAC antibody labelling in P7 and adult hippocampus was largely overlapping with the in situ staining. Western blot analysis showed GABAC receptor in retina, ovary and testis. In the spinal cord the ρ2 signal was consistently stronger than ρ1 with overlapping expression patterns. At P1, the most intensely labelled cells were the motoneurons while on P7 and adult sections, interneurons and motoneurons were likewise labelled. On spinal neurons both ρ1 and ρ2 mRNAs showed somatodendritic localization, extending out for >100 µm with punctate appearance especially in adult cells. A similar spinal distribution pattern was provided with polyclonal antibody labelling, suggesting close correspondence between mRNA and protein compartmentalization. Electrophysiological experiments indicated that P1 spinal motoneurons did possess functional GABAC receptors even though GABAC receptors played little role in evoked synaptic transmission. Our results suggest a pattern of ρ1 and ρ2 subunit distribution more widespread than hitherto suspected with strong developmental regulation of subunit occurrence.
In vivo regulation of dopamine and noradrenaline release by α2A‐adrenoceptors in the mouse prefrontal cortex
Authors: Ihalainen Jouni A. , Tanila Heikki 
Published: March 2003

AbstractThe present study investigated the role of α2A‐adrenoceptor subtype in the regulation of noradrenaline and dopamine release in the medial prefrontal cortex. The effect of local introduction of the α2‐adrenoceptor agonist dexmedetomidine (10−9−10−8 m) on noradrenaline and dopamine release was investigated in α2A‐adrenoceptor knockout and control mice by using in vivo microdialysis. Furthermore, to reveal a possible distinction between regulation of baseline and peak release, we sampled the dialysate during both rest and handling‐induced mild stress. Baseline noradrenaline and dopamine concentrations did not differ between α2A‐adrenoceptor knockout and control mice. Dexmedetomidine decreased, in a concentration‐dependent manner, noradrenaline and dopamine levels in both genotypes. However, the effect of dexmedetomidine on noradrenaline release was attenuated in the α2A‐adrenoceptor knockout mice, whereas the effect on dopamine release did not differ between the genotypes. The first handling episode increased noradrenaline and dopamine levels to the same extent in both genotypes. However, in α2A‐adrenoceptor knockout mice the noradrenaline and dopamine levels remained elevated in the samples following the first handling whilst, in the control mice, transmitter levels returned to baseline levels. In control mice the handling‐induced peak noradrenaline and dopamine levels were lower after the administration of dexmedetomidine than during the first handling episode, but in α2A‐adrenoceptor knockout mice no drug effect on handling‐induced peak noradrenaline and dopamine levels was found. Our results suggest that the release of noradrenaline in the medial prefrontal cortex is mainly regulated via α2A‐adrenoceptors, whilst other α‐adrenoceptor subtypes play a significant role in the regulation of dopamine release.
Differential Ca2+‐dependence of transmitter release mediated by P/Q‐ and N‐type calcium channels at neonatal rat neuromuscular junctions
Authors: Rosato‐Siri Marcelo D. , Piriz Joaquin , Tropper Barbara A. Giugovaz , Uchitel Osvaldo D. 
Published: March 2003

AbstractN‐ and P/Q‐type voltage dependent calcium channels (VDCCs) mediate transmitter release at neonatal rat neuromuscular junction (NMJ). Thus the neonatal NMJ allows an examination of the coupling of different subtypes of VDCCs to the release process at a single synapse. We studied calcium dependence of transmitter release mediated by each channel by blocking with ω‐conotoxin GVIA the N‐type channel or with ω‐agatoxin IVA the P/Q‐type channel while changing the extracellular calcium concentration ([Ca2+]o). Transmitter release mediated by P/Q‐type VDCCs showed steeper calcium dependence than N‐type mediated release (average slope 3.6 ± 0.09 vs. 2.6 ± 0.03, respectively). Loading the nerve terminals with 10 µm BAPTA‐AM in the extracellular solution reduced transmitter release and occluded the blocking effect of ω‐conotoxin GVIA (blockade −2 ± 9%) without affecting the action of ω‐agatoxin IVA (blockade 85 ± 4%). Both VDCC blockers were able to reduce the amount of facilitation produced by double‐pulse stimulation. In these conditions facilitation was restored by increasing [Ca2+]o. The facilitation index (fi) was also reduced by loading nerve terminals with 10 µm BAPTA‐AM (fi = 1.2 ± 0.1). The control fi was 2.5 ± 0.1. These results show that P/Q‐type VDCCs were more efficiently coupled to neurotransmitter release than were N‐type VDCCs at the neonatal neuromuscular junction. This difference could be accounted for by a differential location of these channels at the release site. In addition, our results indicate that space–time overlapping of calcium domains was required for facilitation.
Effects of nursing mothers on rPer1 and rPer2 circadian expressions in the neonatal rat suprachiasmatic nuclei vary with developmental stage
Authors: Ohta Hidenobu , Honma Sato , Abe Hiroshi , Honma Ken‐ichi 
Published: March 2003

AbstractThe ability of nursing mothers to entrain the circadian pacemaker of rat pups was examined by measuring the rat Per1 (rPer1) and rPer2 expression levels in the suprachiasmatic nuclei (SCN). Newborn rats from mothers under a light–dark cycle (LD) were blinded immediately after birth and reared by foster mothers under either LD (LD blind pups) or reversed light–dark cycle (DL; DL blind pups). At postnatal day (P)6, small but significant phase differences were observed in the circadian gene expression rhythms of the SCN not only between the blind and sighted pups, but also between the two groups of blind pups, indicating the involvement of both free‐running and maternal influence in phase‐resetting the circadian rhythms of blind pups. However, from P6 to P13 the circadian rhythms of both LD and DL blind pups showed phase delays of similar extent, which suggests that the influence of nursing mothers was lost. From P13 to P20 (the day of weaning), the rPer1 and rPer2 rhythms phase‐shifted in a different manner, the rPer2 rhythm being related more closely to the behavioural rhythm than was the rPer1. This finding suggests a differential influence of mothers on the rPer1 and rPer2 rhythms in the third week of life. It is concluded that the ability of nursing mothers to entrain pup circadian oscillation depends on the developmental stage.
Synaptic localization of GABAA receptor subunits in the substantia nigra of the rat: effects of quinolinic acid lesions of the striatum
Authors: Fujiyama Fumino , Stephenson F. Anne , Bolam J. Paul 
Published: March 2003

AbstractThe inhibitory amino acid, γ‐aminobutyric acid (GABA), plays a critical role in the substantia nigra (SN) in health and disease. GABA transmission is controlled in part by the type(s) of GABA receptor expressed, their subunit composition and their location in relation to GABA release sites. In order to define the subcellular localization of GABAA receptors in the SN in normal and pathological conditions, sections of SN from control rats and rats that had received quinolinic acid lesions of the striatum were immunolabelled using the postembedding immunogold technique with antibodies against subunits of the GABAA receptor. Immunolabelling for α1, β2/3 and γ2 subunits was primarily located at symmetrical synapses. Double‐labelling revealed that β2/3 subunit‐positive synapses were formed by terminals that were enriched in GABA. Colocalization of α1, β2/3 and γ2 subunits occurred at individual symmetrical synapses, some of which were identified as degenerating terminals derived from the striatum. In the SN ipsilateral to the striatal lesion there was a significant elevation of immunolabelling for β2/3 subunits of the GABAA receptor at symmetrical synapses, but not of GluR2/3 subunits of the AMPA receptor at asymmetrical synapses. It was concluded that fast GABAA‐mediated transmission occurs primarily at symmetrical synapses within the SN, that different receptor subunits coexist at individual synapses and that the upregulation of GABAA receptors following striatal lesions is expressed as increased receptor density at synapses. The upregulation of GABAA receptors in Huntington's disease and its models is thus likely to lead to an increased efficiency of transmission at intact GABAergic synapses in the SN and may partly underlie the motor abnormalities of this disorder.
Donepezil reverses a mnemonic deficit produced by scopolamine but not by perforant path lesion or transient cerebral ischaemia
Authors: Higgins G.A. , Enderlin M. , Fimbel R. , Haman M. , Grottick A.J. , Soriano M. , Richards J.G. , Kemp J.A. , Gill R. 
Published: March 2003

AbstractThe purpose of these studies were threefold. Firstly, to further characterize the effect of perforant path transection on a test of short‐term memory: delayed matching (or nonmatching)‐to‐position [D(N)MTP]. Secondly, to evaluate the effect of a transient cerebral ischaemia in the same task. Both surgical procedures were chosen as they produce a CNS lesion similar to that described in Alzheimer's Disease (AD). Thirdly, the effect of the acetylcholinesterase inhibitor, donepezil (Aricept®, E2020), on the resulting cognitive impairment was studied. Perforant path transection produced a robust, delay‐dependent impairment of choice accuracy in rats performing either a delayed matching‐ or nonmatching‐to‐position task. Sample latency was also reduced following lesion, yet the lesion‐induced impairment was not affected by increasing the response requirement at the sample stage. An 11‐min period of transient ischaemia (two‐vessel occlusion model) resulted in almost complete loss of hippocampal CA1 pyramidal cells and a delay‐dependent impairment in DMTP performance. However, unlike perforant path lesions, this deficit was unstable and declined in magnitude over the experimental period. Increasing the delay interval restored this deficit. Donepezil, at doses that robustly attenuated a scopolamine (0.06 mg/kg s.c.)‐induced DMTP accuracy impairment in naïve, unoperated rats, had no effect against either lesion‐induced impairment. The results are considered in terms of the effectiveness of acetylcholinesterase inhibitors in noncholinergic‐based preclinical cognitive models.
Cannabinoids inhibit excitatory inputs to neurons in the shell of the nucleus accumbens: an in vivo electrophysiological study
Authors: Pistis Marco , Muntoni Anna Lisa , Pillolla Giuliano , Gessa Gian Luigi 
Published: March 2003

AbstractThe nucleus accumbens (NAc) represents a critical site for the rewarding properties of diverse classes of drugs of abuse. Glutamatergic afferents to the NAc are involved in the actions of psychostimulants and opioids, while the potentiation of dopaminergic neurotransmission in the NAc is a common feature of abused drugs, including cannabinoids. Cannabinoid receptors (CB1) are densely expressed in regions that provide excitatory innervation to the NAc, such as the amygdala, the cortex and the hippocampus. Recent in vitro evidence suggests that indeed cannabinoids modulate glutamatergic synapses in the NAc. In this study we recorded extracellularly from neurons in the shell of the NAc which responded to the stimulation of the baso‐lateral amygdala (BLA) or the medial prefrontal cortex (PFC) in urethane anaesthetized rats. BLA or PFC stimulation induced generation of action potentials in NAc neurons. This excitatory effect was strongly inhibited by the synthetic cannabinoid agonists WIN 55212,2 (0.062–0.25 mg/kg, i.v.) and HU‐210 (0.125–0.25 mg/kg, i.v.) or the psychoactive principle of Cannabis delta(9)‐tetrahydrocannabinol (1.0 mg/kg, i.v.). Neither the D1 or D2 dopamine receptor antagonists (SCH23390 0.5–1.0 mg/kg, sulpiride 5–10 mg/kg, i.v.) or the opioid antagonist naloxone (1.0 mg/kg, i.v.) were able to reverse the action of cannabinoids, while the selective CB1 receptor antagonist/reverse agonist SR141716A (0.5 mg/kg, i.v.) fully suppressed the action of cannabinoid agonists, whereas per se had no significant effect. These results provide evidence that cannabinoids, in common with other drugs of abuse, in vivo strongly inhibit the excitability of neurons in the shell of the NAc.