Mapping the cortical representation of the lumbar paravertebral muscles.

OBJECTIVE: The aim of this study was to map the cortical representation of the lumbar spine paravertebral (LP) muscles in healthy subjects. METHODS: Transcranial magnetic stimulation (TMS) was employed to map the cortical representations of the LP muscles at two sites. Stimuli were applied to points on a grid representing scalp positions. The amplitude of motor evoked potentials (n=6) was averaged for each position. RESULTS: The optimal site for evoking responses in the contralateral LP muscles was situated 1cm anterior and 4 cm lateral to the vertex. Ipsilateral responses were evoked from sites lateral to the optimal site for evoking contralateral responses. Contralateral responses were also obtained from areas anterior to the optimal site. CONCLUSIONS: Maps of these muscles can be produced. The results suggest discrete contra- and ipsilateral cortical projections. Anterior sites at which excitation can be evoked may indicate projections arising in the SMA are involved. SIGNIFICANCE: This study provides normative data regarding the cortical representation of the paravertebral muscles and provides a technique for evaluating cortical motor plasticity in patients presenting with spinal pathologies.

Deficit in motor performance correlates with changed corticospinal excitability in patients with chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is characterised by fatigue and musculosketetal pain, the severity of which is variable. Simple reaction times (SRTs) and movement times (SMTs) are slowed in CFS. Our objective is to correlate the day-to-day changes in symptomatology with any change in SRT, SMT or corticospinal excitability. Ten CFS patients were tested on two occasions up to two years apart. Motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the motor cortex were recorded from the thenar muscles. Threshold TMS strength to evoke MEPs was measured to index corticospinal excitability. SRTs and SMTs were measured. The percentage change in both SRTs and SMTs between the two test sessions correlated with the percentage change in corticospinal excitability assessed according to threshold TMS intensity required to produce MEPs. This study provides evidence that changing motor deficits in CFS have a neurophysiological basis. The slowness of SRTs supports the notion of a deficit in motor preparatory areas of the brain.

Corticospinal inhibition appears normal in patients with chronic fatigue syndrome.

The pathogenesis of chronic fatigue syndrome (CFS) remains unknown. Thresholds and latencies of motor evoked potentials (MEPs) in response to transcranial magnetic stimulation (TMS) are normal but intracortical inhibition has not been investigated. Eleven patients with CFS were compared with 11 control subjects. Each patient completed a questionnaire using visual analogue indices of pain, fatigue, anxiety and depression. Subjects released a button to initiate simple (SRTs) and choice reaction time (CRTs) tasks; for each task, movement times were measured between release of the initiation button and depression of a second button 15 cm away. Subjects held a 10 % maximum voluntary contraction in the thenar muscles of their dominant hand while TMS was applied to the motor cortex; the duration and extent of inhibition of surface electromyographic (EMG) activity were assessed at stimulus strengths above and below the threshold for MEPs. Patients had significantly (P < 0.05) higher mean indices of fatigue than of pain, anxiety or depression. Mean (+/- S.E.M.) SRTs (but not CRTs) were longer in patients (309 +/- 45 ms) than in controls (218 +/- 9 ms). Movement times were longer in patients for both SRTs and CRTs. TMS thresholds, expressed as a percentage of the maximum stimulator output, were not significantly (P > 0.05) different in both groups for both MEPs (patients, 34 +/- 3%; controls, 36 +/- 3%) and inhibition of voluntary contraction (patients, 29 +/- 2%; controls, 34 +/- 4%). The duration and extent of inhibition did not differ significantly between groups at any stimulus strength. The pattern of change in duration and extent of inhibition with increasing stimulus intensity was no different in the two groups. The duration and extent of corticospinal inhibition in patients with CFS did not differ from controls, adding further evidence to the notion that the feeling of fatigue and the slowness of movement seen in CFS is not manifest in corticospinal output pathways.

Do oarsmen have asymmetries in the strength of their back and leg muscles?

The aim of this study was to establish whether asymmetry of the strength of the leg and trunk musculature is more prominent in rowers than in controls. Nineteen oarsmen and 20 male controls matched for age, height and body mass performed a series of isokinetic and isometric strength tests on an isokinetic dynamometer. These strength tests focused on the trunk and leg muscles. Comparisons of strength were made between and within groups for right and left symmetry patterns, hamstring: quadriceps ratios, and trunk flexor and extensor ratios. The results revealed no left and right asymmetries in either the knee extensor or flexor strength parameters (including both isometric and isokinetic measures). Knee extensor strength was significantly greater in the rowing population, but knee flexor strength was similar between the two groups. No difference was seen between the groups for the hamstring: quadriceps strength ratio. In the rowing population, stroke side had no influence on leg strength. No differences were observed in the isometric strength of the trunk flexors and extensors between groups, although EMG activity was significantly higher in the rowing population. Patterns of asymmetry of muscle activity were observed between the left and right erector spinae muscles during extension, which was significantly related to rowing side (P < 0.01). These observations could be related to the high incidence of low back pain in oarsmen.

Somatopy of perceptual threshold to cutaneous electrical stimulation in man.

Neurological testing tools for measuring and monitoring somatosensory function lack resolution and are often dependent on the clinician testing. In this study we have measured perceptual threshold (PT) to electrical stimulation of the skin and compared it with two-point discriminative ability (TPDA) in 12 control subjects. Tests were made on both sides of the body at American Spinal Injury Association (ASIA) key points on seven spinal dermatomes (C3 (neck), C4 (shoulder), C5 (upper arm), C6 (thumb), T8 (abdomen), L3 (knee), L5 (foot)) and in the mandibular (chin) and maxillary (cheek) fields of the trigeminal (V) nerve. Electrical stimulation (0.5 ms pulse width; 3 Hz) was applied via a self-adhesive cathode and an anode strapped to the wrist or ankle. The stimulus intensity was adjusted and PT was recorded as the lowest current at which the subject reported sensation. Sites were tested in random order. Indices for both TPDA and PT differed according to the dermatome tested but there was no correlation between TPDA and PT for any dermatome. There was good correlation between results from equivalent dermatomes on left and right sides for both PT and TPDA. Women frequently had lower mean (+/- S.E.) PTs and better TPDA than men; differences were significant (P < 0.05) for PT on the knee (women, 1.31 +/- 0.15 mA; men, 2.05 +/- 0.26 mA) and the foot (women, 2.90 +/- 0.19 mA; men, 4.13 +/- 0.28 mA) and for TPDA on the thumb (women, 3.8 +/- 0.2 mm; men, 7.8 +/- 1.3 mm) and the knee (women, 17.8 +/- 1.6 mm; men, 27.1 +/- 4.0 mm). Four subjects repeated the experiment on another day and the results correlated well with the first test for PT (r2, 0.62) and TPDA (r2, 0.48). PT differs between dermatomes in a predictable way but does not relate to TPDA. PT is easy to measure and may be a useful assessment tool with which to monitor recovery or deterioration in neuropathies, neurotrauma or after surgery.

Corticospinal control of human erector spinae muscles.

We used transcranial magnetic stimulation (TMS) to study corticospinal excitability to erector spinae (ES) muscles during graded voluntary contractions in bilateral trunk extension (BTE) and forced expiratory breath holding (FEBH) in normal individuals. Motor evoked potentials (MEPs) could be produced in all subjects in the absence of voluntary activation. At maximum voluntary contraction, levels of surface electromyographic (EMG) activity were 4 times greater during BTE than FEBH. When EMG was normalized to maximum, MEP amplitudes increased in proportion to contraction in both tasks. MEPs in FEBH were compared with extrapolated values at similar EMG levels in BTE and were found to be larger. EMG and MEPs in left and right ES were symmetrical throughout the range of contractions in both tasks. ES muscles have a facilitation pattern similar to that previously shown in leg muscles, but subtle differences at low levels of EMG suggest that the facilitation is dependent on the task.

Corticospinal facilitation studied during voluntary contraction of human abdominal muscles.

Transcranial magnetic stimulation (TMS) of the human motor cortex was used to study facilitation of motor-evoked potentials (MEPs) in the rectus abdominis (RA) muscle, a trunk flexor, during voluntary activation. MEPs could be produced in the relaxed RA muscles of all six normal subjects studied. The MEPs had short latencies (18-22 ms) which are consistent with other studies suggesting a fast corticospinal input to the trunk muscles. Marked facilitation was observed in the MEPs when subjects were asked to produce graded levels of voluntary contractions. The two tasks used to produce voluntary contractions were a forced expiration during a breath-holding task (FEBH) and bilateral trunk flexion (BTF). Maximal voluntary EMG activity during the BTF task produced around 4.2 times more integrated EMG than during the FEBH task. Similarly the MEP amplitude at MVC was 2.3 times greater during BTF than FEBH. The pattern of MEP facilitation with increasing voluntary EMG was not linear and a maximal MEP amplitude was observed at a level of voluntary contraction around 30 % MVC in both tasks. There were some subtle differences in the pattern of facilitation in the two tasks. When TMS was applied to the right cortex only, MEPs were seen in both left and right RA muscles suggesting some ipsilateral corticospinal innervation. The latency of the right (ipsilateral) response was approximately 2 ms longer than the left. Comparison with studies in hand and leg muscles suggests that the facilitation pattern in RA may reflect a substantial degree of corticospinal innervation. Experimental Physiology (2001) 86.1, 131-136.

Voluntary motor function in patients with chronic fatigue syndrome.

INTRODUCTION: The pathogenesis of chronic fatigue syndrome (CFS) remains unknown. In particular, little is known of the involvement of the motor cortex and corticospinal system. METHODS: Transcranial magnetic stimulation (TMS) was used to assess corticospinal function in terms of latency and threshold of motor-evoked potentials (MEPs) in thenar muscles. Reaction times and speed of movement were assessed using button presses in response to auditory tones. RESULTS: Patients had higher (P<.05) self-assessed indices of fatigue (7/10) than for pain (5/10), anxiety (4/10) or depression (3/10). Mean (+/-S.E.M.) simple reaction times (SRTs) were longer (P<.05) in the patients (275+/-19 ms) than in the controls (219+/-9 ms); choice reaction times (CRTs) were not significantly longer in the patients. Movement times, once a reaction task had been initiated, were longer (P<.05) in the patients in both SRTs (patients, 248+/-13 ms; controls, 174+/-9 ms) and CRTs (patients, 269+/-13 ms; controls, 206+/-12 ms). There was no difference (P>.05) in threshold or latency of MEPs in hand muscles between the patients (threshold, 54.5+/-2.2% maximum stimulator output [% MSO]; latency 22+/-0.3 ms) and controls (threshold 54.6+/-3.6% MSO; latency 22.9+/-0.5 ms). Regression analysis showed no correlation (P>.05) of SRTs with either threshold for MEPs or fatigue index. CONCLUSION: Corticospinal conduction times and excitability were within the normal range despite a slower performance time for motor tasks and an increased feeling of fatigue. This suggests that the feeling of fatigue and the slowness of movement seen in CFS are manifest outside the corticospinal system.

Changes in [Ca2+]i and membrane currents during impaired mitochondrial metabolism in dissociated rat hippocampal neurons.

1. This study was designed to establish the basis for altered membrane excitability during the inhibition of mitochondrial metabolism in central mammalian neurons. Perforated whole-cell patch clamp and fluorimetric techniques were combined to examine changes in membrane currents, intracellular calcium ([Ca2+]i) and mitochondrial potential (DeltaPsim) in neurons dissociated from the CA1 subfield of the hippocampus of young rats. 2. On application of the mitochondrial inhibitor NaCN, or the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), the membrane potential hyperpolarized and membrane conductance increased. Under voltage clamp, an outward current was seen. The reversal potential of the current at -83 mV and its dependence on extracellular [K+] confirmed that this was a K+ conductance. 3. Simultaneous recordings of [Ca2+]i and current showed a striking correlation between a rise in [Ca2+]i and the developed outward current. Flash photolysis of the caged Ca2+ chelator, diazo-2, reversed both the rise in [Ca2+]i and the outward current. The current was reduced by 80 % by charybdotoxin, was attenuated by 10 mM TEA+ but was unaffected by apamin or by the KATP channel blocker tolbutamide (400 microM-1 mM). These data suggest strongly that the current is carried by Ca2+-dependent K+ channels. 4. Simultaneous recordings of membrane current, DeltaPsim and [Ca2+]i revealed the sequence of events in response to impaired mitochondrial function (CN, FCCP or anoxia): DeltaPsim depolarized, followed rapidly by an increase in [Ca2+]i followed in turn by the outward current. [Ca2+]i and membrane current recovered only after mitochondrial repolarization. 5. The rise in [Ca2+]i appeared to result from an increased Ca2+ influx through voltage-gated Ca2+ channels. It was dependent on extracellular Ca2+ and was much reduced by methoxyverapamil (D600). The rate of Mn2+ quench of fura-2 fluorescence was increased by the inhibitors, and the inhibitors induced a small inward current when K+ channels were blocked that preceded the rise in [Ca2+]i. However, the increase in [Ca2+]i showed no obvious dependence on membrane potential in cells clamped at a range of holding potentials from -90 to -45 mV. 6. Thus, removal of oxygen, uncoupling mitochondrial oxidative phosphorylation or inhibition of respiration, all lead to mitochondrial depolarization, an increased Ca2+ influx through (voltage-gated) channels, even at hyperpolarized membrane potentials, raising [Ca2+]i which in turn drives an increased K+ conductance that modulates membrane excitability.

The relationship between mitochondrial state, ATP hydrolysis, [Mg2+]i and [Ca2+]i studied in isolated rat cardiomyocytes.

1. As ATP has a higher affinity for Mg2+ than ADP, the cytosolic magnesium concentration rises upon ATP hydrolysis. We have therefore used the Mg(2+)-sensitive fluorescent indicator Magnesium Green (MgG) to provide an index of changing ATP concentration in single rat cardiomyocytes in response to altered mitochondrial state. 2. In response to FCCP, [Mg2+]i rose towards a plateau coincident with the progression to rigor, which signals ATP depletion. Contamination of the MgG signal by changes in intracellular free Ca2+ concentration (the KD of MgG for Ca2+ is 4.7 microM) was excluded by simultaneous measurement of [Ca2+]i and [Mg2+]i in cells dual loaded with fura-2 and MgG. The response to FCCP was independent of external Mg2+, confirming an intracellular source for the rise in [Mg2+]i. 3. Simultaneous measurements of mitochondrial NAD(P)H autofluorescence and mitochondrial potential (delta psi m; .-1 fluorescence) and of autofluorescence and MgG allowed closer study of the relationship between [Mg2+]i and mitochondrial state. Oligomycin abolished the FCCP-induced rise in [Mg2+]i without altering the change in autofluorescence. Thus, the rise in [Mg2+]i in response to FCCP is consistent with the release of intracellular Mg2+ following ATP hydrolysis by the mitochondrial F1F0-ATPase. 4. The rise in [Mg2+]i was correlated with cell-attached recordings of ATP-sensitive K+ channel (KATP) activity. In response to FCCP, an increase in KATP channel activity was seen only as [Mg2+]i reached a plateau. In response to blockade of mitochondrial respiration and glycolysis with cyanide (CN-) and 2-deoxyglucose (DOG), [Mg2+]i rose more slowly but again KATP channel opening increased only when [Mg2+]i reached a plateau and the cells shortened. 5. Oligomycin decreased the rate of rise of [Mg2+]i delayed the onset of rigor and increased the rate of mitochondrial depolarization in response to CN-_DOG. Thus, with blockade of mitochondrial respiration delta psi m is maintained by the mitochondrial F1F0-ATPase at the expense of ATP reserves. 6. In response to CN-_DOG, the initial rise in [Mg2+]i was accompanied by a small rise in [Ca2+]i. After [Mg2+]i reached a plateau and rigor developed, [Ca2+]i rose progressively. On reperfusion, in hypercontracted cells, [Ca2+]i recovered before [Mg2+]i and [ca2+]i oscillations were sustained while [Mg2+]i decreased. Thus on reperfusion, full recovery of [ATP]i is slow, but the activation of contractile elements and the restoration of [Ca2+]i does not require the re-establishment of millimolar concentrations of ATP.

Characterization of Ca(2+)-activated 86Rb+ fluxes in rat C6 glioma cells: a system for identifying novel IKCa-channel toxins.

1. The pharmacological characteristics of a putative Ca2+ activated K+ channel (IKCa channel) in rat glioma C6 cells were studied in the presence of the Ca2+ ionophore, ionomycin and various K+ channel blockers, 86Rb+ being used as a radioisotopic tracer for K+. 2. The resting 86Rb+ influx into C6 cells was 318 +/- 20 pmol s-1. The threshold for ionomycin activation of 86Rb+ influx was approx. 100 nM. At ionomycin concentrations above the activation threshold, the initial rate of 86Rb+ influx was proportional to ionophore concentration. Ionomycin-activated 86Rb+ flux was saturable (EC50 = 0.62 +/- 0.03 microM) and was not inhibited by ouabain. 3. Intracellular Ca2+ increased within 30 s from a basal level of 42 +/- 2 nM to 233 +/- 17 nM, after addition of 2 microM ionomycin. During this period, intracellular pH fell from 7.03 +/- 0.04 to 6.87 +/- 0.03 and the cell hyperpolarized from -34 +/- 10 mV to -76 +/- 2 mV. 4. Single channel conductance measurements on inside-out patches in physiological K+ solutions identified a 14 +/- 3 pS CA(2+)-activated K+ current between -25 mV and +50 mV. In symmetrical (100 mM) K+, the single channel conductance was 26 pS. 5. Externally applied quinine (IC50 = 0.12 +/- 0.34 mM) and tetraethylammonium chloride (IC50 = 10 +/- 1.9 mM) inhibited 86Rb+ influx into C6 cells in a concentration-dependent manner. Charybdotoxin (IC50 = 0.5 +/- 0.02 nM) and iberiotoxin (IC50 = 800 +/- 150 nM), as well as the crude venoms from the scorpions Leiurus quinquestriatus and Mesobuthus tamulus, also inhibited 86Rb+ influx. In contrast, apamin and toxin I had no inhibitory effects on 86Rb+ flux. A screen of fractions from cation exchange h.p.l.c. of Mesob. tamulus venom revealed the presence of at least four charybdotoxin-like peptides. One of these was iberiotoxin; the other three are novel toxins. 6. The ionomycin-activated 86Rb+ influx into rat C6 glioma cells has proved to be a valuable pharmacological assay for the screening of toxins and crude venoms which modify intermediate conductance, Ca2+ activated K+ channel activity.

The development of GABAB-mediated activity in the rat dentate gyrus.

We examined the effects of GABAB receptor activation in the dentate gyrus of hippocampal slices prepared from 6-8-day-old rat pup. Baclofen (0.25-1.0 microM), a GABAB agonist, rapidly and potently disinhibited the developing dentate, similar to its effect in the mature organism. CGP 35348, a GABAB antagonist, quickly reversed the baclofen-induced disinhibition. However, GABAB antagonists did not reverse long-latency (500-1000 ms IPI) paired-pulse depression, suggesting that it is not caused by a late GABAB-mediated IPSP. GABAB-mediated disinhibition of the dentate gyrus can occur by postnatal day 6, providing a powerful mechanism for altering excitability in the developing hippocampus.

The nitric oxide synthase inhibitor, N-monomethyl-L-arginine blocks induction of a long-term potentiation-like phenomenon in rat medial frontal cortical neurons in vitro.

1. Nitric oxide has been implicated in the production of long-term depression (LTD) in the cerebellum and in the production of long-term potentiation (LTP) and LTD in the hippocampus. We now provide evidence of its involvement in the induction of long-term synaptic potentiation in in vitro slices in the cerebral cortex of the rat. 2. Intracellular recordings were made from layer V neurons in the medial frontal cortex, and excitatory synaptic potentials (EPSPs) were evoked by electrical stimulation of layers II/III. Tetanic stimulation of this pathway may induce LTD or LTP or no change at these synapses. First we established experimental conditions under which a long lasting potentiation could be induced with a high incidence (> 60%), namely perfusion of slices with 1 microM bicuculline methiodide, second the use of increased shock duration in the tetanic conditioning stimuli, third and most important the addition of QX-314 to the microelectrode to reduce potassium conductances. Because the potentiation of the mean EPSP slope was significantly greater than the control at 40-min postconditioning, but was declining throughout this period, we refer to it for brevity as LTP, but strictly class it as an LTP-like phenomenon. 3. The nitric oxide (NO) synthase inhibitor interfered with the production of LTP. In the control group of neurons (n = 13) the mean depolarizing slope of the EPSP at 30-min post-conditioning was 142.7 +/- 2% (mean +/- SE) of the prestimulation control.(ABSTRACT TRUNCATED AT 250 WORDS)

The postsynaptic induction of nonassociative long-term depression of excitatory synaptic transmission in rat hippocampal slices.

1. Long-term depression (LTD) is an activity-dependent reduction in the strength of synaptic transmission that can persist for hours. It is a neural model for processes underlying learning and memory, such as extinction and forgetting. LTD of excitatory postsynaptic potentials (EPSPs) in cells of the CA1 region of hippocampal slices can be induced in an anti-Hebbian paradigm, i.e., by conditioning stimuli that activate the postsynaptic neuron in the absence of evoked synaptic transmission in the test pathway. Past work showed that LTD was not produced consistently in a pharmacologically untreated slice, but it could be induced more reliably when the conditioning stimuli were applied during block of evoked transmitter release. We have now defined further the conditions in which LTD can be obtained using postsynaptic conditioning by investigating 1) whether intracellular conditioning is effective, 2) the requirement for extracellular Ca2+, and 3) the consequences of selective block of glutamate ionotropic receptor subtypes during the conditioning procedure. 2. Intracellular recordings were made from CA1 pyramidal neurons. Test shocks were applied to the stratum radiatum except during conditioning, and the depolarizing slopes and amplitudes of evoked EPSPs were measured. The conditioning procedure activated the postsynaptic neuron either antidromically (via trains of shocks at 100 Hz applied to the axons in the alveus) or intracellularly (via depolarizing pulses of 1.5-3.5 nA). During conditioning, postsynaptic potentials (PSPs) evoked by the conditioning stimuli either were transiently blocked by bathing slices for 5 min in artificial cerebrospinal fluid (CSF) containing a high [Mg2+] or were reduced by glutamate antagonists. 3. When slices were bathed in CSF containing 25 mM Mg2+ and 2 mM Ca2+, evoked PSPs were transiently abolished; conditioning, either by antidromic or intracellular stimulation, always evoked a significant LTD. During the LTD produced by antidromic stimulation, the mean EPSP slope was 52.6 +/- 11.4% (mean +/- SE) of its control at 30-35 min after conditioning (n = 7). The LTD produced by intracellular conditioning was of similar magnitude: the mean EPSP slope was 57.2 +/- 11.6% of its control at 30-35 min postconditioning (n = 7). When slices were bathed in CSF containing 25 mM Mg2+ and 2 mM Ca2+ without conditioning stimuli, there was no LTD (mean EPSP slope 109 +/- 8.1% of its control at 30-35 min after reperfusion with CSF; n = 5).(ABSTRACT TRUNCATED AT 400 WORDS)

Investigation of beta-adrenergic modulation of synaptic transmission and postsynaptic induction of associative LTP in layer V neurones in slices of rat sensorimotor cortex.

Long-term potentiation (LTP) of synaptic transmission is considered to be a neuronal model of learning. Recently, the probability of induction of associative LTP in layer V cells in sensorimotor neocortex was shown to be much higher in the awake cat than in the slice preparation. We hypothesised that the loss of extrinsic noradrenergic activity in the slice might account for this difference, particularly since a beta-adrenergic enhancement of field potentials has been seen in this preparation. We therefore bath-applied noradrenaline (NA) or the beta 1-adrenergic agonist, isoprenaline (ISO) to elucidate the cellular basis of the enhancement of field potentials, and to see if the drugs increased the probability of induction of associative LTP in slices. We found that NA and ISO produced a dose-dependent, reversible reduction of spike accommodation and an increase in excitability but had no effect on the depolarizing slope or peak amplitude of sub-threshold EPSPs, and that drug application did not increase the probability of induction of LTP. We conclude that: (1) the enhancement of field potentials and late components of EPSPs (7) can be explained by the known actions of beta-adrenergic drugs on membrane currents in layer V cells, and (2) the lower probability of induction of associative LTP in slices cf. the awake cat cannot be due solely to the loss of noradrenergic activity.

The modulation of long-term potentiation by delta-9-tetrahydrocannabinol in the rat hippocampus, in vitro.

The duration of long-term potentiation (LTP) of the CA1 evoked field potential in rat hippocampal slices was significantly modulated by pre-treatment of slices with delta-9-tetrahydrocannabinol (THC) added to the incubation media. The three THC doses tested: 10 picomolar (pM), 100 pM, and 1000 pM, resulted in a biphasic change in population spike amplitude, such that 10 pM resulted in an increase, while 100 and 1000 pM resulted in dose-related decreases as compared to the control treatment. Upon subsequent induction of LTP by tetanizing stimulation, the THC treatments resulted in significant changes in the duration but not magnitude of potentiation. The early component of potentiation, post-tetanic potentiation, or PTP, was not affected by the THC treatments. LTP was seen to decay in an exponential manner over the 121 mini post-tetanus monitoring period. For comparisons of LTP duration, therefore, the half-life (t1/2) of LTP was extrapolated from linear regression analysis. The t1/2 values were determined for each treatment group from the slopes of the linear regression analysis of the logarithmically transformed time course data. While the control group t1/2 was determined as 280 min, the t1/2 for the THC groups were: 350 min (10 pM); 91 min (100 pM); and 33 min (1000 pM) doses, respectively. In context with previous reports of the disruptive action of marihuana intoxication on learning and memory, these results suggest that one possible action of THC may be in modulating hippocampal electrophysiology and its role in short-term memory processes.