Biomedical subjects

Malcolm Lidierth

Publications and source records attributed to Malcolm Lidierth.

4 recordsLinked to original sources

PubMed2006

Local and diffuse mechanisms of primary afferent depolarization and presynaptic inhibition in the rat spinal cord.

Two types of dorsal root potential (DRP) were found in the spinal cord of urethane-anaesthetized rats. Local DRPs with short latency-to-onset were evoked on roots close to the point of entry of an afferent volley. Diffuse DRPs with a longer latency-to-onset were seen on more distant roots up to 17 segments from the volley entry zone. The switch to long latency-to-onset occurred abruptly as a function of distance along the cord and could not be explained by conduction delays within the dorsal columns. Long-latency DRPs were also present and superimposed on the short-latency DRPs on nearby roots. Both local and diffuse DRPs were evoked by light mechanical stimuli: von Frey hair thresholds were <or= 1 gram force Changes in excitability of the terminals of sural nerve afferents were used to confirm that both local and diffuse DRPs were associated with primary afferent depolarization (PAD). These effects were potent: the area of the antidromic volley evoked in the sural nerve by intraspinal microstimulation in the L4/5 spinal segment was increased by 109 +/- 50% (mean +/- s.d.; n = 5) by nearby conditioning stimuli, and by 52 +/- 12% (n = 6) with stimuli applied 9-13 mm (5-8 segments) away. The time course of the changes in terminal excitability closely matched those of the DRPs. Reduction of the field potentials evoked in the dorsal horn by stimulation of dorsal roots was also shown to accompany both local and diffuse DRPs. The area of the monosynaptically evoked field potential was reduced by 48 +/- 19% (n = 7) with nearby conditioning stimulation and 16 +/- 9% (n = 10) with stimulation 9-12 mm distant. Evidence is presented that this inhibition includes a presynaptic component. Similar effects were seen with field potentials evoked by sural nerve stimulation. It is concluded that diffuse DRPs are mediated through propriospinal networks which may contribute to the gating of sensory information flow during natural behaviour as they respond to weak mechanical stimuli and provoke presynaptic inhibition.

Action Potentials↗

PubMed2005

Pulser: user-friendly, graphical user-interface based software for controlling stimuli during data acquisition with Spike2 for Windows.

This paper describes software that runs in the Spike2 for Windows environment and provides a versatile tool for generating stimuli during data acquisition from the 1401 family of interfaces (CED, UK). A graphical user interface (GUI) is used to provide dynamic control of stimulus timing. Both single stimuli and trains of stimuli can be generated. The pulse generation routines make use of programmable variables within the interface and allow these to be rapidly changed during an experiment. The routines therefore provide the ease-of-use associated with external, stand-alone pulse generators. Complex stimulus protocols can be loaded from an external text file and facilities are included to create these files through the GUI. The software consists of a Spike2 script that runs in the host PC, and accompanying routines written in the 1401 sequencer control code, that run in the 1401 interface. Handshaking between the PC and the interface card are built into the routines and provides for full integration of sampling, analysis and stimulus generation during an experiment. Control of the 1401 digital-to-analogue converters is also provided; this allows control of stimulus amplitude as well as timing and also provides a sample-hold feature that may be used to remove DC offsets and drift from recorded data.

Action Potentials↗

PubMed2004

Laminar distribution of GABAA- and glycine-receptor mediated tonic inhibition in the dorsal horn of the rat lumbar spinal cord: effects of picrotoxin and strychnine on expression of Fos-like immunoreactivity.

Inhibitory mechanisms are essential in suppressing the development of allodynia and hyperalgesia in the normal animal and there is evidence that loss of inhibition can lead to the development of neuropathic pain. We used Fos expression to map the distribution of tonically inhibited cells in the healthy rat lumbar spinal cord. In a control group, Fos-like immunoreactive (Fos-LI) cells were rare, averaging 7.5+/-2.2 cells (mean+/-SEM; N=13 sections) per 20 microm thick section of dorsal horn. This rose to 103+/-11 (mean+/-SEM; N=20) in picrotoxin-treated rats and to 88+/-11 (mean+/-SEM; N=18) in strychnine-treated rats. These changes were significant (ANOVA; P<0.001). There were marked regional variations in the distribution of Fos-LI cells between picrotoxin- and strychnine-treated animals. Picrotoxin induced a significant increase in the number of Fos-LI cells throughout the dorsal horn (lamina I-VI) while strychnine significantly elevated Fos-like immunoreactivity only in deep laminae (III-VI). For both picrotoxin and strychnine, the increase in Fos-like immunoreactivity peaked in lamina V (at 3579+/-319 and 3649+/-375% of control, respectively; mean+/-SEM) but for picrotoxin an additional peak was observed in the outer part of lamina II (1959+/-196%). Intrathecal administration of both GABAA and glycine receptor antagonists has been shown elsewhere to induce tactile allodynia. The present data suggest that this allodynia could arise due to blockade of tonic GABAA and glycine-receptor mediated inhibition in the deep dorsal horn. GABAA antagonists also induce hypersensitivity to noxious inputs. The blockade of tonic inhibition in the superficial dorsal horn shown here may underlie this hyperalgesia.

Animals↗

PubMed1999

Brief and prolonged effects of Lissauer tract stimulation on dorsal horn cells.

Increased excitability of dorsal horn neurones may play a critical role in producing some pain states and there is evidence that the excitability of neurones lying throughout the dorsal horn is subject to regulation by cells in its most superficial laminae. This paper examines the effect on dorsal horn cell receptive fields and excitability of the specific activation of Lissauer's tract, a tract containing propriospinal axons which arise from cells in the substantia gelatinosa and which project to the substantia of neighbouring spinal segments. Experiments were carried out on anaesthetised spinal rats in the L3-4 spinal segments with microelectrode stimulation on the surface of the Lissauer tract (LT) and microelectrode recording of single cells or small groups of cells that responded to gentle brushing on the skin. Single shocks or brief trains of low-level stimuli to the LT produced a characteristic long-latency dorsal root potential (DRP) on the L3 dorsal root and a brief burst of firing in superficial cells with no stimulation of primary afferents. Generally, this was accompanied by no excitation of deeper dorsal horn cells but commonly by a period of inhibition, often followed by facilitation. We then turned to the effect of long periods (30-90min) of continual LT stimulation because we had seen hints of prolonged facilitation of the deeper cells after periods of such stimulation. Trains of 5 stimuli separated by 2ms and repeated every 200ms were used with individual pulses of 200 micros duration and less than 10 microA amplitude. This resulted in a shift of the effect on deep cells from primarily inhibition to mainly facilitation. We then examined in detail the effect of these long periods of LT stimulation on the size of receptive fields (RFs) of dorsal horn cells first on single units and then by repeated mapping of the RFs of small groups of cells. Control periods of 60min with no LT stimulation produced no significant RF changes but 30, 60 or 90min of LT stimulation produced successively greater expansions of RFs. When the LT stimulus was turned off after 1h, the RFs remained expanded for at least 2h. The spike height of these cells remained unchanged. The effect was not influenced by the NMDA antagonist MK801 but was imitated by the GABA(A) antagonist picrotoxin. It is concluded that the prolonged expansion of RFs could not be produced by modulation of descending control since the animals had spinal transections. Neither was it dependent on an NMDA-sensitive mechanism. With these data it is not possible to conclude whether the mechanism is pre-synaptic, post-synaptic or both. It is proposed that the most likely explanation is a decrease in the normal tonic inhibition operated in part by a GABA dependent mechanism. This phenomenon may play a role in prolonged pathological states of increased spinal cord excitability.

Animals↗