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PubMed2006

Criteria for conduction block based on computer simulation studies of nerve conduction with human data obtained in the forearm segment of the median nerve.

The finding of conduction block (CB) on nerve conduction studies supports the diagnosis of potentially treatable immune-mediated neuropathies. CB in a number of axons may result in reduction of the compound muscle action potential (CMAP) on proximal versus distal stimulation (decrement). Decrement may also result from increased temporal dispersion (TD) as this leads to desynchronization and phase cancellation of the motor unit action potentials (MUAPs) out of which the CMAP is built up; polyphasia of MUAPs possibly yields additional decrement. To prove the occurrence of CB, decrement has to be larger than can be explained by increased TD or increased phase cancellation. This was established previously by simulations using MUAPs recorded in rats assuming maximal TD. Unfortunately, criteria based on human data and criteria for nerves with limited TD are not available. In the present study, criteria for CB were derived using simulations with thenar surface recorded MUAPs affected by collateral reinnervation that were obtained in patients with lower motor neurone disease (LMND). The effect of TD on decrement was determined for a wide range of TDs in the forearm segment of the median nerve and the segment distal to this. Our criteria for CB were based on area decrement because this was less influenced by TD and more by CB than amplitude decrement. The maximal area decrement in the forearm segment increased as TD in the forearm segment increased but decreased as TD in the distal segment increased. This suggests that, when desynchronization and phase cancellation occur in the distal segment due to TD, less phase cancellation and, therefore, less decrement can occur due to TD in the forearm. The finding that duration prolongation on proximal versus distal stimulation reflected TD within the forearm segment and that distal duration reflected TD in the distal segment allowed proposal of a more flexible set of criteria for forearm segments when TD in the forearm segment is limited or TD in the distal segment is pronounced. A separate investigation showed that the maximal TD in chronic inflammatory demyelinating polyneuropathy was within the range of our simulations, indicating that these were realistic. Our criteria were validated retrospectively in patients with multifocal motor neuropathy and patients with LMND. In the forearm segment of the median nerve, our criteria were more sensitive and equally specific for CB as compared with criteria for CB based on the study using rats. Our criteria have to be evaluated prospectively.

Action Potentials↗

PubMed2005

[Multidetector CT for the diagnosis of congenital vascular anomalies and associated complications in newborns and infants].

PURPOSE: To assess the value of multidetector CT (MDCT) for evaluation of vascular anomalies (VA) and associated complications in newborns and infants. MATERIALS AND METHODS: Seventy-five children (mean age: 9 +/- 6 months, range: 2 weeks to 24 months) with VA were examined using MDCT (4-, 8- or 16-row; collimation 0.5-1.25 mm; scan time 7-30 s), which was performed under controlled ventilation or free breathing. Image quality was rated using a 5-point scale. Image findings were correlated to echocardiography, conventional catheter angiography (CCA), bronchoscopy, and intraoperative findings. RESULTS: High quality MDCT data were almost free of cardiac and respiratory motion. In all cases, VA morphology and topography in relation to adjacent structures, e. g. tracheal and esophageal compression caused by an aortic ring, could be assessed exactly and allowed the final diagnosis. Even aberrant vessels, such as aorto-pulmonary collaterals (MAPCA) with a diameter of less than 1 mm, could be identified and excellently visualized. Eighty percent (60/75) of all patients had benefited from the MDCT: in 31 patients CCA was neither necessary to perform surgical planning nor to exclude a VA; in an additional 29 patients radiation doses and sedation time due to interventional procedures could be reduced markedly. CONCLUSIONS: MDCT can now be regarded as the modality of choice as a minimally invasive, robust, and accurate technique for the diagnosis of complex VA, their potentially life-threatening complications and preoperative planning even in newborns and infants. Its accuracy for detecting VA appears equivalent to CCA while it is more accurate in delineating potential life-threatening complications.

Arteriovenous Malformations↗

PubMed2005

Netrin-1 induces axon branching in developing cortical neurons by frequency-dependent calcium signaling pathways.

A single axon can innervate multiple targets by collateral branching. Axon branching is thus essential for establishing CNS connectivity. However, surprisingly little is known about the mechanisms by which branching is regulated. Axons often stop elongating before branches develop and anatomical and molecular data suggest that axon branching occurs independent of axon outgrowth. We found that netrin-1 dramatically increases cortical axon branching. Here, we sought to identify intracellular signaling components involved in netrin-1-induced axon branching. Using live cell imaging of dissociated developing cortical neurons, we show that netrin-1 rapidly increases the frequency of repetitive calcium transients. These transients are often restricted to small regions of the axon. Simultaneous imaging of calcium activity and development of axon branches revealed that Ca2+ transients coincide spatially and temporally with protrusion of branches from the axon. Remarkably, fully formed branches with motile growth cones could develop de novo within 20 min. Netrin-1-induced Ca2+ transients involve release from intracellular stores and Ca2+ signaling is essential for netrin-1-induced axon branching. Using techniques to overexpress or suppress kinase activity, we find that calcium/calmodulin-dependent protein kinase II (CaMKII) and mitogen-activated protein kinase (MAPK) are major downstream targets of the netrin-1 calcium signaling pathway and are required for axon branching. CaMKII, but not MAPK, is also involved in axon outgrowth. The role of CaMKII and MAPKs in axon branching is consistent with the sensitivity of these kinases to changes in the frequency Ca2+ transients. Together, these novel findings define calcium signaling mechanisms required for development of new axon branches promoted by a guidance cue.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1999

Intraspinal and behavioral consequences of nerve growth factor-induced nociceptive sprouting and nerve growth factor-induced hyperalgesia compared in adult rats.

Intraspinal and behavioral events were studied in adult rats with nociceptive nerves that were undergoing collateral sprouting into adjacent denervated skin. This sprouting, which is driven by endogenous nerve growth factor (NGF), did not cause hyperalgesia. For comparison, we studied an exogenous NGF administration that induced hyperalgesia but was too brief to evoke sprouting. When nociceptive nerves sprouted in skin, back-labeling with wheat germ agglutinin-conjugated horseradish peroxidase revealed that their projections sprouted in the cord. The sprouted peripheral nerves now activated more c-Fos-containing interneurons, which stimulus-response studies showed was not due to an increased afferent discharge. We attribute the interneuron recruitment to synaptogenesis following the intraspinal sprouting. Nociceptive stimulation of dorsal skin reflexly activates underlying cutaneous trunci muscle (CTM). When a nociceptive field expanded by nerve sprouting, so did the area of the evoked CTM reflex: this implies a recruitment of CTM motoneurons. We interpret this "matching" of response to stimulus as an adaptive phenomenon ensured by an adaptive intraspinal sprouting of the nociceptive projections. Neither the intraspinal changes nor the reflex changes occurred if peripheral sprouting was blocked by systemic anti-NGF treatment, indicating that the role of endogenous NGF was only in that sprouting. No comparable adaptive events occurred during NGF-induced hyperalgesia. Neither nociceptive fields nor CTM reflexes were affected; however there was a recruitment of c-Fos-expressing interneurons. This recruitment was not explained by peripheral sensitization, and, because sprouting was not involved here, we attribute the recruitment to "synaptic unmasking," i.e., an increased effectiveness of the preexisting excitatory circuitry.

Adaptation, Physiological↗

PubMedDate not supplied

Physiologic and clinical significance of myocardial blood flow quantitation: what is expected from these measurements in the clinical ward and in the physiology laboratory?

In this essay we review data on absolute quantitation of myocardial blood flow (MBF) in humans. Earlier work established that coronary heart disease (CAD) can be detected by coronary angiography and that this disease has characteristic features at rest and during stress, which indicate the linkage between regional metabolic needs and myocardial perfusion. In the 1970s myocardial perfusion was mapped in patients with radioxenon, but this method had significant technical limitations. About the same time, radioactive microspheres were introduced for cardiovascular research and investigations; these particles provided insights on MBF in acute infarction and ischemia, myocardial reperfusion, collateral circulation, myocardial blood flow during exercise, coronary flow reserve (CFR), and layer-to-layer distribution of MBF. Studies with microspheres also permitted investigators to establish the presence in the heart of MBF heterogeneity. Currently, there are several techniques that aim at extending these concepts into clinical investigation. Two of these techniques, i.e. Doppler coronary flow velocity and fast magnetic resonance imaging assess epicardial flow dynamics and CFR. Contrast myocardial echocardiography is another novel technique which has been useful in mapping the area at risk, reperfusion, myocardial viability and collateral circulation. This essay also considers the emerging technique of intracoronary ultrasound which has shown evidence of disease underestimation by conventional contrast angiography. Positron emission tomography (PET) is a noninvasive technique that uniquely and quantitatively maps myocardial perfusion and CFR. The latter can be computed before and after angioplasty. PET studies have further demonstrated that chronic myocardial ischemia does not exist as a distinct state in patients with CAD. From the above investigations the concept has arisen that not only is CAD an entity involving epicardial vessels but also, in a significant portion of patients, an abnormal microcirculation plays an important role in the pathogenesis of ischemic syndromes. PET studies have relatively low spatial resolution since they cannot resolve layer-to-layer absolute MBF.

Animals↗

PubMed2001

[Antecubital flap: advantages in elbow coverage. An anatomical study and experience of five clinical cases].

The antecubital flap is a fasciocutaneous strip that has its blood supply provided by the first proximal collateral of the radial artery. This flap was described for the first time in 1983 by Lamberty and Cormack, but it has not been widely used and there have been only a few reports in the literature concerning this procedure. The aim of the present investigation was to demonstrate via an anatomical study and a report on five cases the viability of the various anatomical features of this cutaneous flap, and also its positive contribution to elbow reconstruction. The anatomical study involved eight fresh cadavers (eight upper limbs). An injection of colored prevulcanized latex was made in the humeral artery in the lower third of the arm. The aim was to determine which artery provided blood supply to the flap, its anatomical location, and also to look for possible distal anastomoses which would permit a distal pedicled flap to be removed. Contrary to the findings of other authors, in the present study it was found that the vessel providing blood to the antecubital flap always branched off from the radial artery. However, no anastomoses with distal vascularization were detected, which would have permitted a distal pedicled flap to be obtained. The use of the antecubital flap for elbow coverage was then illustrated by five clinical cases of soft tissue defects of the elbow. This method was found to be reliable, practical, and the flap could be rapidly dissected. Moreover, this particular technique is sensitive, and has an interesting rotational arc. The distal cutaneous island flap has the advantage of limiting scar tissue. A comparison between the antecubital flap and other pedicled flaps has then been made. In conclusion, it appears that this little-known procedure has definite advantages, and that it should be included in the range of surgical techniques that are available for soft tissue reconstruction in the case of elbow defects.

Adult↗

PubMed2006

Cerebral hemodynamics after contralateral carotid endarterectomy in patients with symptomatic and asymptomatic carotid occlusion: a 10-year follow-up.

We sought to investigate whether carotid endarterectomy (CEA) can achieve long-term cerebral hemodynamic improvement and reduce recurrence of cerebral ischemic events in symptomatic and asymptomatic patients with severe (>70%) carotid artery stenosis contralateral to carotid occlusion (CO). Thirty-nine patients with severe carotid lesion contralateral to CO were studied before (1 day) and after CEA (at 7 days, 1, 3 and 6 months, and then yearly thereafter). Collateral flow and cerebral vasomotor reactivity (VMR) were assessed by transcranial Doppler sonography (TCD). A total of 32 unoperated patients with severe carotid lesion contralateral to CO, who were comparable with respect to age and sex, served as a control group. The average period of TCD follow-up was 10 years and was obtained in all patients; during this period, major clinical events (stroke, acute myocardial infarction and death) were also recorded. The proportion of patients with collateral flow via the anterior communicating artery increased significantly from 61.5% before to 89.7% after CEA (P = 0.01). Cerebral VMR ipsilateral to CO improved in 85.7% of patients (30 of 35) within 30 days of CEA, and in all patients within 90 days. No significant spontaneous VMR recovery was recorded in the control group. After the initial recovery, no significant change in VMR was observed in the surgical group or the control group during the follow-up. In conclusion, in patients with severe carotid stenosis, CEA contralateral to symptomatic and asymptomatic CO determines a durable cerebral hemodynamic improvement not only on the side of the CEA but also on the contralateral side, with no difference between symptomatic and asymptomatic patients.

Aged↗

PubMed1999

Projections of the dorsal motor nucleus of the vagus to cardiac ganglia of rat atria: an anterograde tracing study.

We injected the anterograde fluorescent tracer 1,1'-dioleyl-3,3,3',3'-tetramethylindocarbocyanine methanesulfonate (DiI) into the dorsal motor nucleus of the vagus (DmnX), counterstained the cardiac ganglia with Fluorogold (FG), and used confocal microscopy to examine the distributions and different types of DmnX fibers in wholemounts of the atria. We also quantified the number of DmnX cardiac axons and the number of innervated cardiac principal neurons (PNs). Rats with unilateral DiI injections were used in three different experiments, including unilateral FG soaking of cervical vagal trunks, intracranially rhizotomizing the vagal afferent roots, or contralaterally sectioning the cervical vagus. These manipulations indicated that DiI-labeled cardiac fibers were exclusively from the DmnX. Our observations established that: (1) three major ganglionic plexuses were localized in the epicardium; (2) both sides of the DmnX supplied significant fibers to each of the plexuses; (3) these cardiac efferents formed dense basket terminals around individual PNs; (4) collaterals of individual DmnX fibers diverged, producing calyx endings on multiple PNs; (5) small intensely fluorescent (SIF) cells in the cardiac plexuses were innervated pericellularly; (6) individual axons could innervate both PNs and SIF cells; (7) the total number of DmnX fibers were in the range of [68, 96; left] and [67, 115; right]; (8) these fibers innervated 709 (left) and 494 (right), or at least 18% and 12%, of the PNs, respectively; and (9) vagal preganglionics exhibited a degree of lateralization: Significantly more PNs were contacted by fiber varicosities in the sinoatrial plexus than in the atrioventricular plexus after right DmnX injections. In summary, the present observations suggest that the DmnX plays a significant role(s) in controlling the heart.

Animals↗

PubMed1998

Sympathetic and sensory axons invade the brains of nerve growth factor transgenic mice in the absence of p75NTR expression.

Collateral sprouting, a nerve growth factor (NGF)-mediated growth response of undamaged peripheral axons, can be divided into reparative and aberrant axonal growth. We have previously shown that aberrant growth occurs in transgenic mice overexpressing NGF centrally under the control of the glial fibrillary acidic protein promoter. Both sympathetic and sensory fibers, stained immunohistochemically for tyrosine hydroxylase and calcitonin gene-related peptide, respectively, invade the cerebellum of postnatal transgenic mice, whereas no such axons are seen in age-matched wild-type cerebellum. Recent examination of mice possessing a null mutation for p75NTR has suggested that axon growth may be influenced by the functional expression of this receptor. To address the potential role of p75NTR in axon growth, we have generated a new line of hybrid mice overexpressing NGF but lacking functional p75NTR expression. Postnatal (day 14) hybrid cerebellum possessed fewer aberrant sensory and sympathetic fibers compared to their age-matched transgenic counterparts. By adulthood, however, hybrid cerebellum displayed a robust plexus of axons stained immunohistochemically for calcitonin gene-related peptide and tyrosine hydroxylase. No neuronal or nonneuronal localization of p75NTR-immunoreactive elements was observed in postnatal and adult hybrid cerebellum. Interestingly, sympathetic axons within the hybrid cerebellum displayed a markedly reduced axon density and staining intensity for NGF, suggesting a possible alteration in axonal sequestration of NGF. These results show that p75NTR is not vital for new growth of NGF-sensitive sympathetic and sensory axons and that immunohistochemical detection of NGF at sympathetic axons requires the functional expression of p75NTR.

Animals↗

PubMed2003

Heterotopic ossification after knee dislocation: the predictive value of the injury severity score.

OBJECTIVE: To determine the relationship of multiple variables, including the Injury Severity Score (ISS), closed head injury (CHI), and timing and type of surgery to formation of motion-limiting heterotopic ossification (HO) following knee dislocation. DESIGN: Longitudinal observational study. SETTING: University level 1 trauma center. PATIENTS/PARTICIPANTS: Thirty-five consecutive patients with 36 knee dislocations (OTA fracture and dislocation classification 40-D) admitted over a 26-month period. MAIN OUTCOME MEASUREMENTS: Admission ISS, Glasgow Coma scale (GCS) scores, CHI, timing (> or < 3 weeks from injury) and type (open or arthroscopic) of surgery, number of cruciate ligaments reconstructed, medial surgical procedure, and eventual presence or absence of motion-limiting HO. RESULTS: A classification system for HO was developed ranging from none (type 0) to ankylosing (type IV) HO. Twenty-nine patients with type 0-III HO recovered an average range of motion of 126 degrees at an average of 14 months (group A). Six patients formed ankylosing type IV HO (group B). The ISS in group A ranged from 9 to 26. ISS in group B ranged from 26 to 50 (P < 0.001). Regarding the formation of type IV HO, the sensitivity of an ISS >/=26 was 100%, the specificity was 97%, and the positive predictive value was 86%. Patients in group B had a greater incidence of documented CHI (P < 0.025). Timing and type of surgery, number of ligaments reconstructed, and whether or not the patient had a medial surgical procedure had no statistical influence on degree of HO formation. CONCLUSIONS: An ISS of 26 seems to be a discrete boundary above which patients with knee dislocation are at extremely high risk for type IV HO formation if undergoing surgical reconstruction and below which patients are likely spared this complication. The presence of a CHI is a significant factor in type IV HO formation, although harder to quantify. None of the remaining independent variables studied were significantly related to ankylosing type IV HO formation.

Anterior Cruciate Ligament Injuries↗

PubMed1991

Mechanism of enlargement of major cerebral collateral arteries in rabbits.

Major cerebral collateral arteries enlarge following bilateral ligation of the common and internal carotid arteries. The purpose of this investigation was to determine the relative contribution of cellular hypertrophy versus cellular hyperplasia to this vessel change in a morphometric analysis as well as the functional properties of remodeled vessels in an in vitro study. We assessed cell number and vessel dimensions by morphometric analysis of 16 perfusion-fixed rabbit basilar arteries. Results demonstrated significant increases in luminal diameter from 761 to 946 microns (p less than 0.01), medial cross-sectional area from 5.1 x 10(4) to 7.6 x 10(4) micron2 (p less than 0.005), smooth muscle cell volume from 9.19 x 10(5) to 1.44 x 10(6) micron3 (p less than 0.0005), and overall arterial length from 17.41 to 20.36 mm (p less than 0.005) in basilar arteries from the eight ligated rabbits compared with the eight sham-operated controls. Smooth muscle cell volume fraction and cell numerical density were unchanged whereas the number of cells per unit length of artery was increased significantly from 21.5 to 31.0 cells/micron (p less than 0.05). These data indicate that smooth muscle cell hyperplasia rather than hypertrophy contributes to increases in vessel mass. Functional properties of the basilar arteries from 10 ligated and 10 normal control rabbits were analyzed in vitro. Results showed increased contraction to potassium chloride (approximately 74%) (p less than 0.01) and increased sensitivity of smooth muscle to acetylcholine (p less than 0.05) while maximal relaxation was the same as control in the ligated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed2003

Effect of varying chromophores used in light-activated protein solders on tensile strength and thermal damage profile of repairs.

Clinical adoption of laser tissue welding (LTW) techniques has been beleaguered by problems associated with thermal damage of tissue and insufficient strength of the resulting tissue bond. The magnitude of these problems has been significantly reduced with the incorporation of indocyanine green (ICG)-doped protein solders into the LTW procedure to form a new technique known as laser tissue soldering (LTS). With the addition of ICG, a secondary concern has arisen relating to the potential harmful effects of the degradation products of the chromophore upon thermal denaturation of the protein solder with a laser. In this study, two different food colorings were investigated, including blue #1 and green consisting of yellow #5 and blue #1, as alternative chromophores for use in LTS techniques. Food coloring has been found to have a suitable stability and safety profile for enteral use when heated to temperatures above 200 degrees C; thus, it is a promising candidate chromophore for LTS which typically requires temperatures between 50 degrees C and 100 degrees C. Experimental investigations were conducted to test the tensile strength of ex vivo repairs formed using solders doped with these alternative chromophores in a bovine model. Two commonly used chromophores, ICG and methylene blue (MB), were investigated as a reference. In addition, the temperature rise, depth of thermal coagulation in the protein solder, and the extent of thermal damage in the surrounding tissue were measured. Temperature rise at the solder/tissue interface, and consequently the degree of solder coagulation and collateral tissue thermal damage, was directly related to the penetration depth of laser light in the protein solder. Variation of the chromophore concentration such that the laser light penetrated to a depth approximately equal to half the thickness of the solder resulted in uniform results between each group of chromophores investigated. Optimal tensile strength of repairs was achieved by optimizing laser and solder parameters to obtain a temperature of approximately 65 degrees C at the solder/tissue interface. The two alternative chromophores tested in this study show considerable promise for application in LTS techniques, with equivalent tensile strength to solders doped with ICG or MB, and the potential advantage of eliminating the risks associated with harmful byproducts.

Animals↗

PubMed1994

Membrane properties and synaptic responses of interneurons located near the stratum lacunosum-moleculare/radiatum border of area CA1 in whole-cell recordings from rat hippocampal slices.

1. The membrane properties and synaptic inputs of interneurons, located at the stratum (s.) lacunosum-moleculare and radiatum border (L-M) of the CA1 region, were examined with the use of current-clamp whole-cell recordings in rat hippocampal slices. 2. Biocytin-labeled L-M interneurons had nonpyramidal somata and aspinous, often beaded, dendrites that arborized in s. lacunosum-moleculare and radiatum, sometimes as far as s. moleculare of the dentate gyrus. Their axon coursed and branched in s. lacunosum-moleculare and radiatum. Axon collaterals were also observed traversing the hippocampal fissure and arborizing in s. moleculare of the dentate gyrus and s. radiatum of the CA3 region. 3. Several membrane properties of interneurons were typically nonpyramidal: they had large input resistances, short-duration action potentials followed by prominent fast afterhyperpolarizations, and responded to hyperpolarizing current pulses with little membrane rectification. L-M interneurons showed significant anodal break responses, and their mean membrane time constant was 33 ms. After-depolarizations elicited by subthreshold depolarizing current pulses were larger in amplitude and decayed more slowly at depolarized than hyperpolarized membrane potentials. 4. The majority of L-M interneurons (35 of 49 cells) were silent at resting membrane potentials, whereas other displayed either spontaneous single action potentials (n = 12) or rhythmic bursts (n = 2). The rhythmic bursts were insensitive to the N-methyl-D-aspartate (NMDA) and non-NMDA excitatory amino acid receptor antagonists, 2-amino-5-phosphonopentanoic acid (AP-5; 50 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 microM), respectively. Both spontaneous single action potentials and burst firing were blocked by membrane hyperpolarization, suggesting that they were intrinsically rather than synaptically generated. 5. L-M interneurons responded with regular sustained firing to depolarizing current pulses at resting membrane potential. However, at more hyperpolarized membrane potentials (near -75 mV), depolarizing current pulses elicited action-potential firing with a delayed onset. This suggests that voltage-sensitive, transient outward currents may be activated in L-M interneurons from hyperpolarized membrane potentials. 6. Electrical stimulation of s. radiatum or lacunosum-moleculare elicited predominantly long-duration excitatory postsynaptic potentials (EPSPs; n = 20 cells), or both EPSPs and inhibitory postsynaptic potentials (IPSPs; n = 17 cells). In most L-M interneurons (35/37), with increasing intensities, up to two action potentials were elicited. Occasionally, larger bursts (3-5 action potentials) were observed (n = 2). 7. The multiphasic components of the synaptic responses became more evident when stimulations were repeated at different membrane potentials.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1998

Net interaction between different forms of short-term synaptic plasticity and slow-IPSPs in the hippocampus and auditory cortex.

Paired-pulse plasticity is typically used to study the mechanisms underlying synaptic transmission and modulation. An important question relates to whether, under physiological conditions in which various opposing synaptic properties are acting in parallel, the net effect is facilitatory or depressive, that is, whether cells further or closer to threshold. For example, does the net sum of paired-pulse facilitation (PPF) of excitatory postsynaptic potentials (EPSPs), paired-pulse depression (PPD) of inhibitory postsynaptic potentials (IPSPs), and the hyperpolarizing slow IPSP result in depression or facilitation? Here we examine how different time-dependent properties act in parallel and examine the contribution of gamma-aminobutyric acid-B (GABAB) receptors that mediate two opposing processes, the slow IPSP and PPD of the fast IPSP. Using intracellular recordings from rat CA3 hippocampal neurons and L-II/III auditory cortex neurons, we examined the postsynaptic responses to paired-pulse stimulation (with intervals between 50 and 400 ms) of the Schaffer collaterals and white matter, respectively. Changes in the amplitude, time-to-peak (TTP), and slope of each EPSP were analyzed before and after application of the GABAB antagonist CGP-55845. In both CA3 and L-II/III neurons the peak amplitude of the second EPSP was generally depressed (further from threshold) compared with the first at the longer intervals; however, these EPSPs were generally broader and exhibited a longer TTP that could result in facilitation by enhancing temporal summation. At the short intervals CA3 neurons exhibited facilitation of the peak EPSP amplitude in the absence and presence of CGP-55845. In contrast, on average L-II/III cells did not exhibit facilitation at any interval, in the absence or presence of CGP-55845. CGP-55845 generally "erased" short-term plasticity, equalizing the peak amplitude and TTP of the first and second EPSPs at longer intervals in the hippocampus and auditory cortex. These results show that it is necessary to consider all time-dependent properties to determine whether facilitation or depression will dominate under intact pharmacological conditions. Furthermore our results suggest that GABAB-dependent properties may be the major contributor to short-term plasticity on the time scale of a few hundred milliseconds and are consistent with the hypothesis that the balance of different time-dependent processes can modulate the state of networks in a complex manner and could contribute to the generation of temporally sensitive neural responses.

Animals↗

PubMed1996

Associative synaptic plasticity in hippocampal CA1 neurons is not sensitive to unpaired presynaptic activity.

1. Hebbian or associative synaptic plasticity has been proposed to play an important role in learning and memory. Whereas many behaviorally relevant stimuli are time-varying, most experimental and theoretical work on synaptic plasticity has focused on stimuli or induction protocols without temporal structure. Recent theoretical studies have suggested that associative plasticity sensitive to only the conjunction of pre- and postsynaptic activity is not an effective learning rule for networks required to learn time-varying stimuli. Our goal in the current experiment was to determine whether associative long-term potentiation (LTP) is sensitive to temporal structure. We examined whether the presentation of unpaired presynaptic pulses in addition to paired pre- and postsynaptic activity altered the induction of associative LTP. 2. By using intracellular recordings from CA1 pyramidal cells, associative long-term potentiation (LTP) was induced in a control pathway by pairing a single presynaptic pulse with postsynaptic depolarization every 5 s (50-70 x). The experimental pathway received the same training, with additional unpaired presynaptic pulses delivered in close temporal proximity, either after or before associative pairing. Five separate sets of experiments were performed with intervals of -200, -50, +50, +200, or +800 ms. Negative intervals indicate that the unpaired presynaptic pulse was presented before the depolarizing pulse. Our results showed that the presence of unpaired presynaptic pulses, occurring either before or after pairing, did not significantly alter the magnitude of LTP. 3. The experimental design permitted an analysis of whether changes in paired-pulse facilitation (PPF) occur as a result of associative LTP. The average degree of PPF was the same before and after LTP. However, there was a significant inverse correlation between the initial degree of PPF and the degree of PPF after LTP. There was no relationship between the change in PPF, and whether the first or second pulse had been paired with depolarization. 4. These results indicate that the presence of unpaired presynaptic pulses does not alter the induction of synaptic plasticity, suggesting that plasticity of the Schaffer collateral-CA1 synapse is primarily conjunctive rather than correlative.

Animals↗

PubMed2005

Estrogen receptor-alpha and -beta immunoreactive neurons in the brainstem and spinal cord of male and female mice: relationships to monoaminergic, cholinergic, and spinal projection systems.

For many populations of estrogen-sensitive neurons it remains unknown how they are associated with central nervous system circuitries that mediate estrogen-induced modulation of behavioral components. With the use of double-labeling immunohistochemistry and tracing techniques, the relationships of estrogen receptor (ER)-alpha- and ER-beta-immunoreactive (IR) neurons in the mouse brainstem and spinal cord to monoaminergic, cholinergic, and spinal projection systems are explored. Similar distributions of ER-IR neurons were present in females and males, with differences in labeling intensity of ER-alpha immunoreactivity among males and estrogen-, and oil-treated females. Barrington's nucleus, the ventrolateral medulla, and the nucleus of the solitary tract contained spinal-projecting ER-alpha-IR neurons, whereas ER-alpha-IR neurons in the periaqueductal gray, parabrachial nucleus, and catecholaminergic A1 cell group received spinal input. Numerous tyrosine hydroxylase (TH)-IR ER-alpha-IR neurons were present in the ventral periaqueductal gray, nucleus of the solitary tract, A1 cell group, and lumbosacral cord. The dorsal raphe nucleus contained ER-alpha-IR and ER-beta-IR neurons that colocalized with serotonin (5HT), and the reticulotegmental nucleus contained 5HT-IR ER-alpha-IR neurons. Fibers IR for vesicular acetylcholine transporter (VAChT), TH, and 5HT were located among ER-alpha-IR neurons in the dorsal horn and spinal autonomic regions. Robust staining for TH and VAChT, but not 5HT, was present among ER-alpha-IR neurons in the lumbosacral lateral collateral pathway. Possible modulatory actions of estrogen on each of these ER-IR populations are discussed in the context of their specific function, including micturition, sexual behavior, ejaculation, cardiovascular and respiratory control, tactile and nociceptive sensory processing, anti-nociception, endocrine regulation, and feeding.

Animals↗

PubMedDate not supplied

Advantages of continuous electroencephalographic monitoring during carotid artery surgery.

One hundred carotid endarterectomies were performed using selective shunting based on continuous electroencephalographic monitoring (CEM) for the detection of cortical ischemia. Changes associated with ischemia were loss of frequency and amplitude. The results of CEM were correlated with carotid stump pressure (CSP) measurements. Only one (4%) of the 25 patients who developed an abnormal EEG had a mean CSP greater than 50 mmHg: however, CEM was positive in only 24 (45%) of the 53 patients with a CSP less than 50 mmHg. Using EEG as a standard, no CSP criterion (50 or 25 mmHg) was sufficiently sensitive and specific to recommend its routine use (50 mmHg--96% and 61% respectively; 25 mmHg--40% and 96% respectively). Operative mortality was 1%. The three intraoperative neurologic deficits (3%), one transient and two permanent, are analyzed with respect to the operative EEG findings. In the 100 endarterectomy patients and three more undergoing carotid exploration or excision of carotid body tumor EEG changes due to anesthetic problems not associated with carotid clamping were often identified. In 48 additional endarterectomies a computerized display and disk storage of six selected EEG leads, each with a reference trace for comparison, has provided information equivalent to that from the full EEG. EEG monitoring is more accurate than CSP measurement for identifying patients who require shunting, safely dispensing with a shunt in many cases which would otherwise be shunted by standard CSP criteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2001

Blockade of long-term potentiation by beta-amyloid peptides in the CA1 region of the rat hippocampus in vivo.

The effect of intracerebroventricular (icv) injections of beta-amyloid peptide fragments Abeta[15-25], Abeta[25-35], and Abeta[35-25] were examined on synaptic transmission and long-term potentiation (LTP) in the hippocampal CA1 region in vivo. Rats were anesthetized using urethan, and changes in synaptic efficacy were determined from the slope of the excitatory postsynaptic potential (EPSP). Baseline synaptic responses were monitored for 30 min prior to icv injection of Abeta peptides or vehicle. High-frequency stimulation (HFS) to induce LTP was applied to the Schaffer-collateral pathway 5 min or 1 h following the icv injection. HFS comprised 3 episodes of 10 stimuli at 200 Hz, 10 times, applied at 30-s intervals. Normal LTP measured 30 min following HFS, was produced following icv injection of vehicle (191 +/- 17%, mean +/- SE, n = 6) or Abeta[15-25; 100 nmol] (177 +/- 6%, n = 6) 1 h prior to HFS. LTP was, however, markedly reduced by Abeta[25-35; 10 nmol] (129 +/- 9%, n = 6, P < 0.001) and blocked by Abeta[25-35; 100 nmol] (99 +/- 6%, n = 6, P < 0.001). Injection of the reverse peptide, Abeta[35-25], also impaired LTP at concentrations of 10 nmol (136 +/- 3%, n = 6, P < 0.01) and 100 nmol (144 +/- 7, n = 8, P < 0.05). Using a different protocol, HFS was delivered 5 min following Abeta injections, and LTP was measured 1 h post HFS. Stable LTP was produced in the control group (188 +/- 15%, n = 7) and blocked by Abeta[25-35, 100 nmol] (108 +/- 15%, n = 6, P < 0.001). A lower dose of Abeta[25-35; 10 nmol] did not significantly impair LTP (176 +/- 30%, n = 4). The Abeta-peptides tested were also shown to have no significant effect on paired pulse facilitation (interstimulus interval of 50 ms), suggesting that neither presynaptic transmitter release or activity of interneurons in vivo are affected. The effects of Abeta on LTP are therefore likely to be mediated via a postsynaptic mechanism. This in vivo model of LTP is extremely sensitive to Abeta-peptides that can impair LTP in a time- ([25-35]) and concentration-dependent manner ([25-35] and [35-25]). These effects of Abeta-peptides may then contribute to the cognitive deficits associated with Alzheimer's disease.

Amyloid beta-Peptides↗