Biomedical subjects

Christopher A Reid

Publications and source records attributed to Christopher A Reid.

7 recordsLinked to original sources

PubMed2006

The mechanism of carbamazepine aggravation of absence seizures.

Carbamazepine (CBZ) aggravates many generalized seizures types, particularly absence seizures, but the mechanisms underlying this are poorly understood. GABA signaling within the reticular nucleus (Rt) and the ventrobasal complex (VB) of the thalamus is critical to the neurophysiology of absence seizures. The hypothesis that CBZ aggravates absence seizures by acting at the VB thalamus via a GABA(A) receptor-mediated mechanism was investigated in a genetic rat model, generalized absence epilepsy rats from Strasbourg (GAERS). Seizure activity was quantified by a 90-min electroencephalogram recording postdrug injection. Intracerebroventricular injections of CBZ (15 microg in 4 microl) resulted in seizure aggravation versus vehicle treatment, with a mean increase in seizure time of 40%. This indicates that CBZ acts directly, rather than via a metabolite, on the brain to aggravate seizures. Seizure aggravation also occurred following bilateral microinjection of CBZ (0.75 microg in 0.2 microl) into the VB (53%) but not following injection into the Rt (-9%). However, seizure aggravation was blocked when the GABA(A) receptor antagonist, bicuculline (BIC, 0.04 microg in 0.2 microl), was coinjected with CBZ into the VB. Injection of BIC alone (versus vehicle) into the VB also blocked seizure aggravation following systemic administration of CBZ (15 mg/kg i.p.). In vitro studies in Xenopus oocytes expressing recombinant GABA(A) receptors demonstrated that CBZ produced a dose-dependent potentiation of the GABA current at a physiological relevant concentration range (1-100 microM). These data demonstrate that CBZ acts at the VB thalamus to aggravate absence seizures in GAERS and that activation of GABA(A) receptors is critical to this effect.

Animals↗

PubMed2006

Null mutation of the alpha4 nicotinic receptor subunit increases the propensity of muscarinic-mediated neuronal bursting in mouse hippocampal slices.

Alpha4 subunit nicotinic cholinergic receptor (nAChR) knock out mice (KO) have a greater susceptibility to proconvulsant-induced seizures than do wild type (WT). The underlying mechanisms remain obscure. We tested whether such seizure-like activity was reflected in bursting activity of hippocampal neurons by recording with intracellular microelectrodes from CA1 pyramidal neurons in slices from WT and KO mice. Intriguingly, while carbachol-induced bursting activity occurred in only 21% of WT slices, qualitatively identical patterns of bursting occurred in 72% of KO slices. Extracellular recordings from CA1 and CA3 regions suggest that carbachol-mediated population activity was regionalized in our preparations. The relative weighting of excitatory to inhibitory synaptic potentials was similar between WT and alpha4 KO mice. However, burst-firing cells had a smaller input time constant than non-bursters. Low-concentration DHbetaE (selective alpha4beta2 nAChR antagonist) did not increase the propensity of WT slices to burst-fire, indicating that absence of alpha4 subunits per se, cannot explain the differences in activity between slices from WT and KO mice. These observations suggest that alpha4 nAChRs are unlikely to be involved in modulating the pattern of bursting neural activity, but their absence could induce subtle developmental changes in the sensitivity of hippocampal circuits to develop this behaviour.

Action Potentials↗

PubMed2004

Optical quantal analysis indicates that long-term potentiation at single hippocampal mossy fiber synapses is expressed through increased release probability, recruitment of new release sites, and activation of silent synapses.

It is generally believed that long-term potentiation (LTP) at hippocampal mossy fiber synapses between dentate granule and CA3 pyramidal cells is expressed through presynaptic mechanisms leading to an increase in quantal content. The source of this increase has remained undefined but could include enhanced probability of transmitter release at existing functional release sites or increases in the number of active release sites. We performed optical quantal analyses of transmission at individual mossy fiber synapses in cultured hippocampal slices, using confocal microscopy and intracellular fluorescent Ca(2+) indicators. Our results indicate that LTP is expressed at functional synapses by both increased probability of transmitter release and recruitment of new release sites, including the activation of previously silent synapses here visualized for the first time.

Animals↗

PubMed2004

Systemic hypertension associated with venovenous extracorporeal membrane oxygenation for pediatric respiratory failure.

BACKGROUND/PURPOSE: Arterial hypertension (HTN) is common in neonates on venoarterial (VA) extracorporeal membrane oxygenation (ECMO), but HTN in pediatric venovenous (VV) ECMO has not been well described. The authors noted HTN in their VV ECMO experience and hypothesized that HTN was associated with fluid status, steroid use, and renal insufficiency. METHODS: Records of 50 patients receiving VV ECMO for respiratory failure were reviewed. HTN was defined as systolic blood pressure greater than 95th percentile for age for > or =1 hour, unresponsive to sedation/analgesia. Hypertensive index (HI) is defined as total hypertensive hours per total ECMO hours. Fluid status was estimated by a fluid index (FI = total fluid balance during ECMO per ECMO hours per weight). RESULTS: Forty-seven of 50 patients (94%) had HTN. Median HI was 0.21 (range, 0.01 to 1.0). Thirteen patients had renal insufficiency, 39 received steroids, and 23 received continuous venovenous hemofiltration (CVVH). There was no association between HI and FI, steroid use, or renal insufficiency. Thirty-three patients were treated for HTN, often requiring multiple agents. Bleeding complicated the course of 18 patients, and HI was significantly higher in those patients (P = .03). HI was not different between survivors (37 of 39 with HTN) and nonsurvivors (10 of 11 with HTN). CONCLUSIONS: Hypertension is a common complication associated with VV ECMO with unclear etiology. HTN was frequently difficult to control. This study emphasizes the need for the development of treatment protocols to decrease the incidence, severity, and associated morbidity. Improved insight into the etiology of HTN associated with pediatric VV ECMO, including evaluation of the renin-angiotensin system, would help guide therapy.

Adolescent↗

PubMed2003

Optical quantal analysis reveals a presynaptic component of LTP at hippocampal Schaffer-associational synapses.

The mechanisms by which long-term potentiation (LTP) is expressed are controversial, with evidence for both presynaptic and postsynaptic involvement. We have used confocal microscopy and Ca(2+)-sensitive dyes to study LTP at individual visualized synapses. Synaptically evoked Ca(2+) transients were imaged in distal dendritic spines of pyramidal cells in cultured hippocampal slices, before and after the induction of LTP. At most synapses, from as early as 10 min to at least 60 min after induction, LTP was associated with an increase in the probability of a single stimulus evoking a postsynaptic Ca(2+) response. These observations provide compelling evidence of a presynaptic component to the expression of early LTP at Schaffer-associational synapses. In most cases, the store-dependent evoked Ca(2+) transient in the spine was also increased after induction, a novel postsynaptic aspect of LTP.

Animals↗

PubMed2003

Presynaptic Ca2+ channels: a functional patchwork.

A key step in the release of neurotransmitter is the entry of Ca(2+) into the presynaptic terminal via voltage-activated Ca(2+) channels. N-type and P/Q-type Ca(2+) channels play a predominant role but, surprisingly, their distribution across presynaptic terminals lacks any apparent order. They form a patchwork: at some terminals only N-type channels contribute to transmitter release and in others only P/Q-type channels contribute, but in many terminals both sub-types are active. The physiological implications of this non-uniform distribution are starting to emerge. Recent studies reveal that G-protein-mediated depression of N-type channels is stronger than that of P/Q-type channels, whereas voltage-dependent relief of inhibition is more pronounced for P/Q-type channels. The patchwork distribution of Ca(2+) channel subtypes might therefore enable terminal-specific modulation of transmitter release, enhancing the power of synaptic processing.

Animals↗

PubMed2002

The role of dendritic spines: comparing the complex with the simple.

Since Cajal first observed dendritic spines as 'small thorns' projecting from the dendrites of cerebellar Purkinje cells over a hundred years ago, there has been continued debate on the role of these structures. Over 90% of excitatory synapses connect dendritic spines within the central nervous system, implying their functional importance. No fewer than 20 hypotheses have been proposed for the function of dendritic spines. These range from a simple mechanism for increasing the surface area of excitatory synaptic contacts, to a neuroprotective role. This review compares the two morphologically distinct spine types found on CA3 pyramidal neurons. We compare the similarities and differences displayed by these spines in compartmentalising Ca(2+) and discuss a potential role for the morphologically complex spines found on CA3 pyramidal neurons.

Animals↗