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C E Stafstrom

Publications and source records attributed to C E Stafstrom.

At least 55 records · Page 3Linked to original sources
PubMed1993

Effects of kindling on subsequent learning, memory, behavior, and seizure susceptibility.

To determine the long-term effects of seizures on the developing brain we kindled 20-, 40-, and 60-day-old rats to stage 5 seizures and then elicited an additional 15 seizures using the same kindling stimulation. At age 80 days, all animals that reached stage 5 kindling, and their respective age-matched controls, underwent behavioral testing using the Morris water maze, open field test, and handling test. Prior to euthanasia the animals had seizure threshold tested using flurothyl inhalation. No differences were noted in time to platform in the water maze or activity level in the open field test between the kindled rats and controls in any of the three age groups. Rats kindled at age 20 and 40 were more emotional than the controls in the handling test. In the flurothyl inhalation test, rats kindled at 40 and 60 days of age had a shorter latency to all seizures stages than the controls. These results demonstrate that while kindling results in no alteration of learning, memory, or activity level, it does result in altered emotionality and activity level in immature animals, as well as reduced seizure threshold in pubescent and mature rats. The animal model used appears to be an important variable in determining the long-term effects of seizures.

Administration, Inhalation↗
PubMed1993

MK801 pretreatment reduces kainic acid-induced spontaneous seizures in prepubescent rats.

MK801 is a noncompetitive blocker of N-methyl-D-aspartate receptors which has antiepileptic properties. To evaluate whether MK801 pretreatment in immature rats affects the future spontaneous recurrent seizure (SRS) rate or seizure susceptibility in a model of limbic epilepsy, MK801 (0.2 or 1.0 mg/kg, i.p.) or saline was administered to prepubescent rats 30 min prior to kainic acid (KA; 10 mg/kg, i.p.). With or without MK801 pretreatment, KA caused prolonged status epilepticus. SRS rate over the next 4 weeks, as assessed by intermittent video monitoring, was significantly lower in MK801 treated rats than in those which received KA alone. In addition, fewer MK801 treated rats (43%) developed SRS than those which got KA alone (88%). Susceptibility to generalized seizures was then tested using the volatile convulsant flurothyl; at both doses of MK801, flurothyl seizure latency was significantly greater in pretreated animals. These results show that MK801 pretreatment prior to KA induced status epilepticus reduces subsequent SRS frequency and flurothyl seizure susceptibility, while not substantially altering the acute epileptogenic effects of KA.

Animals↗
PubMed1993

Posterior fossa abnormalities in children with infantile spasms.

In order to explore possible pathophysiologic involvement of the brain stem in infantile spasms, we retrospectively compared clinical and electroencephalographic (EEG) features of 14 children with infantile spasms who had gross posterior fossa abnormalities on neuroimaging studies with 84 children with infantile spasms who had either normal neuroimaging (n = 19) or supratentorial abnormalities (n = 65). Children with posterior fossa abnormalities how lower mean initial and follow-up developmental quotients compared to those with normal imaging or supratentorial abnormalities alone. Age of onset of infantile spasms, latency to treatment, response to steroids, and follow-up EEG pattern were not significantly different among the three groups. Six children (6%) had Dandy-Walker cysts, an association rarely reported with infantile spasms. We conclude that the presence of posterior fossa abnormalities in patients with infantile spasms portends a relatively poor developmental outcome.

Age of Onset↗
PubMed1993

Epilepsy in Down syndrome: clinical aspects and possible mechanisms.

Although epilepsy is more common in persons with trisomy 21 (Down syndrome) than in the general population, the mechanisms by which seizures are generated in this population have received little attention. It is likely that this increased seizure susceptibility is due to a combination of medical risk factors and inherent neurologic abnormalities characteristic of Down syndrome. In this review clinical aspects of seizures among individuals with Down syndrome were described and possible mechanisms by which the trisomy 21 brain may generate seizures were explored.

Adolescent↗
PubMed1992

Behavioral effects of continuous hippocampal stimulation in the developing rat.

There is controversy as to whether prolonged seizures are more detrimental to the immature than the mature brain. To evaluate this question continuous hippocampal stimulation was used to induce prolonged limbic seizures in 20-, 30- and 60-day-old rats. The long-term effects on learning and activity level were then studied at age 80 days using the Morris water maze, a test of spatial learning and memory, and the open field test, a test of an animal's reaction to a novel environment. Limbic status epilepticus in 60-day-old but not 20- and 30-day-old rats caused long-term impairment of learning in the Morris water maze. No differences were noted between the control and the experimental animals in the open field test. These results suggest that the age of seizure onset is an important determinant of long-term cognitive sequelae.

Animals↗
PubMed1992

Kainic acid seizures in the developing brain: status epilepticus and spontaneous recurrent seizures.

Acute and chronic effects of seizures induced by intraperitoneal (i.p.) injection of kainic acid (KA) were studied in developing rats (postnatal days (P) 5, 10, 20, 30, and adult 60). For 3 months following KA-induced status epilepticus, spontaneous recurrent seizure (SRS) occurrence was quantified using intermittent video monitoring. Latency to generalized seizures was then tested using flurothyl, and brains were histologically analyzed for CA3 lesions. In P5-10 rats, KA caused generalized tonic-clonic ('swimming') seizures. SRS did not develop, and there was no significant difference between control and KA-treated rats in latency to flurothyl-induced seizures. In contrast, rats P20 and older exhibited limbic automatisms followed by limbic motor seizures which secondarily generalized. Incidence and frequency of SRS increased with age. P20-30 rats with SRS had shorter latencies to flurothyl seizures than did KA-treated P20-30 rats without SRS or controls. KA-treated P60 rats (with or without SRS) had shorter latencies than controls to flurothyl seizure onset. SRS in P60 rats occurred sooner after KA than in P20-30 rats. CA3 lesions were seen in P20-60 rats with and without SRS, but not in P5-10 rats. These data suggest that there are developmental differences in both acute and chronic responses to KA, with immature animals relatively protected from the long-term deleterious effects of this convulsant.

Aging↗
PubMed1991

Seizures in children with Down syndrome: etiology, characteristics and outcome.

Of 737 patients with Down syndrome, newborn to 22 years of age, 47 had a history of at least one seizure. Of those, 24 children had seizures with an identifiable etiology, usually related to a common medical complication of Down syndrome: neonatal hypoxia-ischemia, hypoxia from congenital heart disease, or infection. These acute medical illnesses may precipitate seizures in brains already predisposed to hyperexcitability because of abnormal neuronal development. It is recommended that all Down syndrome children with seizures undergo investigations to determine the etiology of the seizure.

Adolescent↗
PubMed1988

Multiple potassium conductances and their functions in neurons from cat sensorimotor cortex in vitro.

1. Potassium conductances were studied in large layer V neurons using an in vitro slice preparation of cat sensorimotor cortex. The kinetics and pharmacological sensitivity of K+ currents were studied directly using single microelectrode voltage clamp and indirectly by evoking single or multiple spikes and recording the spike repolarization and subsequent afterhyperpolarizations (AHPs). 2. A fast-decaying afterhyperpolarization (fAHP) and a subsequent medium-duration afterhyperpolarization (mAHP) followed a single spike. The amplitude and duration of the mAHP increased when multiple spikes were evoked at a fast rate (e.g., 100 Hz), and a slower afterhyperpolarization (sAHP) appeared only after sustained repetitive firing. 3. All AHPs were reduced by membrane potential hyperpolarization and raised extracellular K+ concentration, suggesting they were caused by an increased K+ conductance. Only the mAHP and sAHP reversed at the estimated value of potassium equilibrium potential (-100 mV), whereas the mean reversal potential of the fAHP was nearly identical to the mean value of resting potential (-71 mV). 4. Mechanisms underlying spike repolarization, the fAHP, and the mAHP were investigated. Two rapidly activating outward currents, a fast-inactivating current and a slowly inactivating delayed rectifier, were detected by voltage clamp. Both currents were reduced rapidly by tetraethylammonium (TEA). The fast transient current was reduced slowly after divalent cations were substituted for Ca2+ (through a mechanism unrelated to blockade of Ca2+ channels), whereas the delayed rectifier was unaffected. 5. Spike duration was increased and the fAHP was abolished only by blocking agents that reduced the fast outward currents. Effects of extracellular and intracellular TEA were similar. Effects of TEA and Ca2+-free perfusate were additive and resembled the effects of intracellular Cs+. The addition of apamin, d-tubocurare, or Cd2+ was ineffective. We conclude that the two fast outward currents reflect pharmacologically and kinetically separate K+ conductances that are primarily responsible for spike repolarization and the fAHP. 6. Voltage-clamp studies revealed two additional outward currents, which were persistent and Ca2+-mediated. Each current activated and deactivated slowly, but the kinetics of one component were approximately 10 times slower than the other. The decay of these currents gave rise to AHPs resembling the mAHP and the early sAHP. 7. Neither the mAHP nor the sAHP was reduced by TEA. The mAHP was reduced when divalent cations were substituted for Ca2+ or when Cd2+, apamin, or d-tubocurare were added.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1985

Properties of persistent sodium conductance and calcium conductance of layer V neurons from cat sensorimotor cortex in vitro.

Properties of the persistent sodium conductance and the calcium conductance of layer V neurons from cat sensorimotor cortex were examined in an in vitro slice preparation by use of a single microelectrode, somatic voltage clamp, current clamp, intra- and extracellular application of blocking agents, and extracellular ion substitution. The persistent sodium current (INaP) attained its steady level within 2-4 ms of a step change in voltage at every potential where it could be examined directly [to about 40 mV positive to resting potential (RP)]. Because of its fast onset INaP can be activated during a single excitatory postsynaptic potential (EPSP) and can influence the subsequent voltage time course and cell excitability. Application of a depolarizing holding potential greater than or equal to 20 mV positive to RP could inactivate spikes, thus allowing examination of INaP at voltages positive to spike threshold. At every potential where INaP was visible, it was mixed with a slow outward current. After depressing potassium currents with blocking agents, INaP could be observed during depolarizations to about 40 mV positive to RP where it is normally hidden by the larger outward currents. Indirect evidence suggests that INaP is present and large during prolonged depolarizations greater than 50 mV positive to RP. INaP was blocked by intracellular injection of the lidocaine derivative QX-314, as well as by extracellular tetrodotoxin (TTX). INaP was much more sensitive to QX-314 than was the height and rate of rise of the spike. This observation and the results in paragraph 3 above are best explained by separate INaP and spike sodium channels. After blockade of INaP and sodium spikes, Ca2+ spikes could be evoked only if potassium currents were first depressed. The Ca2+-dependent nature of the regenerative potentials was indicated by their disappearance when Co2+ or Mn2+ was substituted for Ca2+ in the perfusate and by the appearance of greatly enhanced potentials of similar form when Ba2+ was substituted for Ca2+. Ba2+ substitution greatly enhanced evoked and spontaneous synaptic potentials. Prolonged-plateau action potentials could be evoked in the presence of TTX and Ba2+. Ca2+ spike threshold was 30-40 mV positive to RP, which is significantly more positive than sodium spike threshold. Results of voltage clamp in the normal perfusate and in the presence of Ca2+-blockers or Ba2+ indicated that little or no Ca2+ conductance is activated in the voltage range 25 mV positive to RP where INaP is the dominant ionic current.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Hyperpolarizing potentials in guinea pig hippocampal CA3 neurons.

There is a bewildering variety of hyperpolarizing potentials which control activity in hippocampal pyramidal cells. These include an inhibitory postsynaptic potential (IPSP) with early and late components, voltage- and calcium-dependent potassium conductances, a voltage-dependent potassium conductance modulated by muscarinic agents (the M-current), and a complex and poorly understood afterhyperpolarization following epileptiform bursts. In hippocampal CA3 pyramidal cells, mossy fiber stimulation elicits an IPSP which is made up of two readily separable components. Using the in vitro slice preparation, we investigated the underlying ionic basis of these IPSP components and compared them to other hyperpolarizing potentials characteristic of the CA3 neurons. Intracellular recordings were obtained and then tissue was exposed to bathing medium low in chloride concentration or high in potassium concentration; the ion "blockers" EGTA (intracellular); tetraethylammonium (TEA) (intra- and extracellular), and barium and cobalt (extracellular); and the gamma-aminobutyric acid (GABA)/chloride antagonists penicillin, bicuculline and picrotoxin.

Animals↗
PubMed1984

Properties of subthreshold response and action potential recorded in layer V neurons from cat sensorimotor cortex in vitro.

Properties of the action potential and subthreshold response were studied in large layer V neurons in in vitro slices of cat sensorimotor cortex using intracellular recording and stimulation, application of agents that block active conductances, and a single-microelectrode voltage clamp (SEVC). A variety of measured parameters, including action-potential duration, afterpotentials, input resistance, rheobase, and membrane time constant, were similar to the same parameters reported for large neurons from this region of cortex in vivo. Action-potential amplitudes and resting potentials were greater in vitro. Most measured parameters were distributed unimodally, suggesting that these parameters are similar in all large layer V neurons irrespective of their axonal termination. The voltage response to subthreshold constant-current pulses exhibited both time and voltage dependence in the great majority of cells. Current pulses in either the hyperpolarizing or subthreshold depolarizing direction cause the membrane potential to attain an early peak and then decay (sag) to a steady level. On termination of the pulse, the membrane response transiently overshoots resting potential. Plots of current-voltage relations demonstrate inward rectification during polarization on either side of resting potential. Subthreshold inward rectification in the depolarizing direction is abolished by tetrodotoxin (TTX). The ionic currents responsible for subthreshold rectification and sag were examined using the SEVC. Steady inward rectification in the depolarizing direction is caused by a persistent, subthreshold sodium current (INaP) (54). Sag observed in response to a depolarizing current pulse is due to activation of a slow outward current, which superimposes on and partially counters the persistent sodium current. Both sag in response to hyperpolarizing current pulses and rectification in the hyperpolarizing direction are caused by a slow inward "sag current" that is activated by hyperpolarizing voltage steps. The sag current is unaltered by TTX, tetraethylammonium, (TEA), Co2+, Ba2+, or 4-aminopyridine. Fast-rising, short-duration action potentials can be elicited by an intracellular current pulse or by orthodromic or antidromic stimulation. Spikes are blocked by TTX. The form of the afterpotential following a directly evoked spike varies among cells with similar resting potentials. Biphasic afterhyperpolarizations (AHPs) with fast and slow components were most frequently seen. About 30% of the cells displayed a depolarizing afterpotential (DAP), which was often followed by an AHP. Other cells displayed a purely monophasic AHP.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗
PubMed1984

Repetitive firing in layer V neurons from cat neocortex in vitro.

Input-output relations of large neurons from layer V of cat sensorimotor cortex were studied in an in vitro slice preparation using steps and ramps of intracellularly injected current. Depolarization attained during the interspike interval (ISI) was compared to the voltage levels required to activate a previously described (29) persistent sodium current (INaP). INaP was studied using a single-electrode voltage clamp in the same cells tested for firing behavior. Following an injected current step, firing rate declined smoothly to a steady level with a time course that was approximately exponential in most cells (tau, 9-43 ms). In most cells, the relation between firing rate and injected current (f-I relation) consisted of two linear segments, both for adapted, steady firing and for early intervals during adaptation. The slope of the steeper, initial (or sole) linear segment of the f-I curve averaged 26.2 Hz/nA during steady firing and was steeper when plotted for early interspike intervals. The variation of the depolarization at which spike initiation occurred (firing level) and the membrane potential between rhythmic spikes was examined during adaptation and steady firing. In most cells, firing level rose rapidly during a rhythmic train to a steady value. The steady firing level attained remained unchanged over a wide range of steady firing rates. Nevertheless, the mean depolarization during the interspike interval (V) increased approximately linearly with steady firing rate. Even at the slowest firing rates, V is sufficient to activate INaP. The use of injected current ramps demonstrated that neocortical cells were sensitive to rate of change of stimulus current (dI/dt) as well as its amplitude (I). The use of ramps followed by steady currents demonstrated that the repetitive response lagged behind changes in stimulus parameters and did not reach a steady state even during slow ramps; i.e., the response depended on time as well as on I and dI/dt. Instantaneous firing rate during the ramp increased linearly with time for a wide range of ramp slopes (dI/dt). The instantaneous firing rate of early interspike intervals was also linearly related to ramp slope for small ramp slopes. In spite of these linear relationships, quantitative analysis indicated that firing rate during ramp stimulation cannot, in general, be described by a simple linear combination of separate amplitude- and rate-dependent terms. The repetitive firing properties of the in vitro neurons are compared to those of in vivo neocortical neurons and other cell types.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1984

Cable properties of layer V neurons from cat sensorimotor cortex in vitro.

The passive cable properties of neurons from layer V of cat neocortex were studied in an in vitro slice preparation using current-clamp techniques and a single-microelectrode voltage clamp. Neurons were examined in the presence and absence of several agents that block time- and voltage-dependent conductances. The charging response to an injected current pulse was well fitted by a single exponential in 12 of 17 cells examined. By itself, this result would suggest that most of the neurons are isopotential. However, the existence of a nonisopotential region was demonstrated in all neurons examined using two alternative, independent methods: application of voltage-clamp steps and current impulses. The decay of the capacitive charging transient following a voltage-clamp step reflects charge redistribution solely in the nonisopotential region and had a mean time constant about 17% of the membrane time constant, tau m. The voltage decay following a current impulse was always fitted by (at least) two exponentials, the shorter of which was about 9% of tau m. These results suggest that a nonisopotential region exists but is electrotonically short, of relatively low-input conductance, or both, independent of a particular neuron model. Adopting Rall's (23, 24) idealized neuron model (isopotential compartment attached to a finite-length uniform cable) resulted in a mean value for the equivalent electrotonic length (L) of the nonisopotential compartment of 0.72 space constants from voltage-clamp data and 1.21 space constants from impulse-response data. A dendrite-to-soma conductance ratio (p) of 2-4 was obtained from either procedure. There were no significant differences in the cable parameters between normal cells and those where conductance-blocking agents were present. A specific membrane resistance (Rm) ranging from 2,300 to 11,700 omega X cm2 was estimated by assuming values of specific membrane capacitance reported in the literature. We conclude that large layer V neocortical neurons in vitro are electrotonically compact in the voltage range near resting potential and in the absence of significant tonic synaptic input. In this respect, their electrotonic cable properties resemble those of other mammalian neurons in vitro.

Animals↗
PubMed1983

Multiple actions of N-methyl-D-aspartate on cat neocortical neurons in vitro.

The potent excitatory amino acid receptor agonist, N-methyl-D-aspartate (NMDA), was applied to cat neocortical neurons in an in vitro slice preparation. NMDA evokes a slow depolarization with a net input conductance decrease, repetitive firing, rhythmic depolarization shifts and bi-stable membrane potential behavior. Use of blocking agents, ion substitution and voltage clamp indicates that NMDA induces a highly voltage-dependent TTX-resistant inward sodium current which accounts for much of the NMDA response.

Animals↗
PubMed1982

Negative slope conductance due to a persistent subthreshold sodium current in cat neocortical neurons in vitro.

The voltage dependent ionic currents of large layer V neurons of cat sensory/motor cortex were examined in an in vitro slice preparation using a single-microelectrode voltage clamp. These cells exhibit a persistent inward current in a voltage range below spike threshold. This inward current is responsible for the increase of input resistance upon depolarization seen in these cells in response to a constant current pulse and is activated at the same voltages traversed by the membrane potential between spikes during rhythmic firing. The inward current appears to be a persistent sodium current, since it is unaffected by extracellular Ba2+ or Co2+ but is blocked by extracellular TTX or intracellular QX314.

Animals↗