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S Alford

Publications and source records attributed to S Alford.

29 records · Page 2Linked to original sources
PubMed1991

Co-localized GABA and somatostatin use different ionic mechanisms to hyperpolarize target neurons in the lamprey spinal cord.

gamma-Aminobutyric acid (GABA) and somatostatin are co-localized in cells close to the central canal in the lamprey. These cells project to the lateral margin of the spinal cord where they form a GABA and somatostatin containing plexus. Stretch receptor neurons (edge cells) are situated along the lateral margin of the spinal cord and their dendrites extend into the GABA and somatostatin containing plexus. To investigate whether GABA and/or somatostatin exert an affect on edge cells, these putative transmitters were applied from extracellular pipettes onto edge cells during intracellular recordings. Both GABA and somatostatin hyperpolarized the edge cells but through different ionic mechanisms. GABA activated a chloride current while somatostatin activated a current most likely carried by potassium which, however, could not be blocked by any of the conventional potassium blockers.

Animals↗
PubMed1991

Long-term potentiation of NMDA receptor-mediated synaptic transmission in the hippocampus.

Neurotransmission at most excitatory synapses in the brain operates through two types of glutamate receptor termed alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors; these mediate the fast and slow components of excitatory postsynaptic potentials respectively. Activation of NMDA receptors can also lead to a long-lasting modification in synaptic efficiency at glutamatergic synapses; this is exemplified in the CA1 region of the hippocampus, where NMDA receptors mediate the induction of long-term potentiation (LTP). It is believed that in this region LTP is maintained by a specific increase in the AMPA receptor-mediated component of synaptic transmission. We now report, however, that a pharmacologically isolated NMDA receptor-mediated synaptic response can undergo robust, synapse-specific LTP. This finding has implications for neuropathologies such as epilepsy and neurodegeneration, in which excessive NMDA receptor activation has been implicated. It adds fundamentally to theories of synaptic plasticity because NMDA receptor activation may, in addition to causing increased synaptic efficiency, directly alter the plasticity of synapses.

Animals↗
PubMed1991

The involvement of GABAB receptors and coupled G-proteins in spinal GABAergic presynaptic inhibition.

GABA acts as a presynaptic inhibitory transmitter in the spinal cord. In the lamprey, it has recently been shown that it acts in this way at both primary sensory and motor system synapses and is important in the generation of a locomotor rhythm. Both GABAA and GABAB receptors are activated at these sites by GABA released during physiological activity. In some systems, GABAB receptor activation has been shown to lead to modulation of ion channel function indirectly through the action of a pertussis toxin (PTX)-sensitive G-protein. Here we have studied the mechanism of action of the presynaptic GABAB receptor in this system. GABAB receptor activation leads to a decrease in axonal membrane impedance and also to a reduction in the axonal action potential duration. The ionic basis for this response remains unknown, though it is not, unlike the response to GABAA receptor activation, mediated by an increase in conductance to Cl-. The effects of GABAB receptor antagonism with phaclofen are mimicked by pretreatment of the spinal cord with PTX. Because this procedure inactivates certain classes of G-proteins, it seemed likely that the GABAB receptor-mediated effects are initiated via a presynaptic population of PTX-sensitive G-proteins. Experiments in which only presynaptic G-proteins were interfered with indicate that this is so. Stable analogs of GTP and GDP were used to activate permanently or to antagonize, respectively, the GTP binding site in the presynaptic component of these spinal synapses. We conclude that GABAB receptor-mediated synaptic suppression in the spinal cord is caused by GTP binding to presynaptic G-proteins linked to the GABAB receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effects of bicuculline and strychnine on synaptic inputs to edge cells during fictive locomotion.

Edge cells are mechanoreceptive neurones located in the lateral tracts of the lamprey spinal cord. Phasic activation of these cells by lateral bending can entrain the activity of the locomotor central pattern generator. During fictive locomotion induced by bath-applied NMDLA (N-methyl-D,L-aspartate) or sensory stimulation, edge cells receive synaptic input. In this paper we provide evidence that the tonic inhibition received during sensory-induced fictive locomotion is glycinergic. We also show that during fictive locomotion induced by application of NMDLA to the spinal cord, bicuculline unveils phasic synaptic activity in edge cells. During sensory-evoked fictive locomotion, by contrast, only tonic synaptic activity is apparent in the presence of bicuculline.

Action Potentials↗
PubMed1990

CNQX and DNQX block non-NMDA synaptic transmission but not NMDA-evoked locomotion in lamprey spinal cord.

The motor pattern underlying locomotion in the lamprey is activated and maintained by excitatory amino acid neurotransmission. The quinoxalinediones 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) are potent and selective antagonists of non-N-methyl-D-aspartate (NMDA) receptors in the mammalian central nervous system. In the lamprey, these compounds are now shown to block fast excitatory synaptic potentials elicited in neurones of the spinal ventral horn. They selectively antagonise responses to the application of selective kainate and quisqualate receptor agonists (kainate and alpha-amino-3-hydroxy-5-methyl-4-isoxalone (AMPA)) but do not influence NMDA receptor-mediated responses. Additionally, it is shown that the activation of NMDA receptors is sufficient to elicit and maintain fictive locomotion after blockade of non-NMDA receptors with either DNQX or CNQX. Conversely, activation of quisqualate receptors with AMPA, but not quisqualate leads to fictive locomotion with properties much like that activated by kainate.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1990

GABAergic control of rhythmic activity in the presence of strychnine in the lamprey spinal cord.

Rhythmic ventral root activity has been induced in the spinal cord of the lamprey in vitro in the presence of strychnine. Bicuculline (a GABAA blocker) increases the initial frequency and decreases the episode duration of such activity, whereas diazepam (which potentiates GABA action) has the opposite effect. In addition, bicuculline slows the depolarisation of ventral horn neurones. However, voltage clamp at potentials positive to the interburst potential does not reveal net outward current, even in the presence of diazepam, indicating that the effects of GABA on the rhythmic activity must be presynaptic to the impaled cells.

Action Potentials↗
PubMed1989

Excitatory neurotransmission activates voltage-dependent properties in neurons in spinal motor system of lamprey.

1. Ventral horn neurons were studied under voltage clamp during episodes of sensory-evoked rhythmic coactivation in the in vitro lamprey spinal cord-tailfin preparation in the presence of strychnine. 2. Voltage clamp under a range of holding potentials during episodes of rhythmic coactivation revealed inward currents coincident with ventral root bursting in the same hemisegment and an apparent reversal potential of about -10 mV. 3. The current-voltage relationship of the peak inward current during each burst of this activity demonstrated a marked voltage dependency. 4. The voltage dependence of the inward current was eliminated by the specific NMDA-receptor blocker, APV, and by removal of Mg2+ from the bathing solution. 5. At depolarized potentials a long-lasting outward current could be observed, indicating an apparent voltage-dependent conductance for K+ and/or Cl-. This current was also blocked by APV and increased by the removal of Mg2+. 6. These results provide evidence that during rhythmic coactivation in strychnine, endogenous release of excitatory amino acid transmitter induces nonlinear conductance properties in ventral horn neurons by the activation of NMDA receptors. The results provide additional evidence that such activation contributes to the membrane potential oscillations that underlie rhythmic locomotory activity.

Animals↗
PubMed1989

Endogenous activation of glycine and NMDA receptors in lamprey spinal cord during fictive locomotion.

Strychnine is shown to abolish left-right alternation in fictive locomotion induced by sensory stimulation. Robust rhythmic activity, characterized by left-right coactivation at each segmental level, is seen in the presence of strychnine at all doses used (0.5-20 microM). The proportion of the cycle occupied by the ventral root bursts and the rostral-caudal coordination is similar to that seen in the absence of strychnine. Furthermore, the rhythm is abolished by cis-2,3-piperidine dicarboxylic acid (PDA), 2-amino-5-phosphonovalerate (APV), or the removal of Mg2+ from the perfusate, as in the absence of strychnine. Voltage clamp was applied to ventral horn neurons during stimulation in the presence of strychnine, with holding potentials negative to the plateau potential associated with a ventral root burst but positive to the potential in the interburst. Inward current was seen during the ventral root burst, but no outward current was seen at burst termination or during the interburst. The results indicate that in fictive locomotion induced by endogenous release of NMDA receptor agonists, left-right alternation is dependent on glycinergic transmission. Furthermore, evidence is provided that in the absence of glycinergic transmission, burst termination may depend on NMDA receptor-linked voltage-sensitive processes.

Animals↗
PubMed1987

Inhibitory synaptic input to edge cells during fictive locomotion.

Edge cells are stretch receptors with receptive fields in the lateral margin of the lamprey spinal cord. Their activity may entrain the spinal central pattern generator (CPG). We have recorded intracellularly from edge cells during short episodes of fictive locomotion. Every cell tested exhibited numerous chloride-sensitive IPSPs. We have therefore provided evidence that edge cell sensitivity is modulated by the activity of the spinal CPG.

Animals↗
PubMedDate not supplied

Ca2+ and synaptic plasticity.

A major effort in neuroscience is directed towards understanding the roles of Ca2+ signalling in the induction of synaptic plasticity. Here, we summarize the evidence concerning Ca2+ signalling, paying particular attention to CA1 excitatory synapses, and its relationship to the induction of long-term potentiation and long-term depression. We discuss the ways in which synaptic activation can elevate Ca2+ postsynaptically and how dendritic spines may act as a Ca2+ compartment which can both isolate and integrate Ca2+ signals.

Animals↗