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D A McCormick

Publications and source records attributed to D A McCormick.

At least 55 records · Page 3Linked to original sources
PubMed1995

Role of the ferret perigeniculate nucleus in the generation of synchronized oscillations in vitro.

1. The cellular mechanisms by which neurons of the ferret perigeniculate nucleus (PGN) participate in the generation of spindle waves and slowed absence seizure-like oscillations were investigated with intracellular and extracellular recording techniques in geniculate slices maintained in vitro. 2. During spindle wave generation, PGN neurons generated repetitive (2-9 Hz) high frequency (up to 500 Hz) burst discharges mediated by the activation of a low threshold Ca2+ spike by the arrival of barrages of excitatory postsynaptic potentials (EPSPs). In most PGN cells at resting membrane potentials (-60 to -70 mV) spindle waves were associated with a progressive hyperpolarization that persisted as a prolonged after-hyperpolarization. 3. The EPSPs occurring in PGN cells were highly synchronized with burst firing in the neighbouring portion of the dorsal lateral geniculate nucleus (LGNd) and were intermixed with short duration inhibitory postsynaptic potentials (IPSPs). After block of GABAergic receptors, the EPSPs occurring during the generation of spindle waves reversed polarity at around 0 mV. In addition, these EPSPs were completely blocked with the bath application of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), as was spindle wave generation in both the PGN and LGNd. 4. Slowing the intraspindle frequency to 2-4 Hz with pharmacological block of GABAA receptors resulted in a marked increase in the intensity of burst firing by PGN cells such that the number of action potentials per burst increased from a maximum of thirteen to a maximum of sixty. Block of GABAA receptors also resulted in a marked increase in the amplitude and duration of the EPSP barrages arriving from the relay laminae during generation of the slowed oscillation. 5. These findings indicate that spindle waves are generated in the ferret LGNd in vitro through an interaction between the GABAergic neurons of the PGN and relay neurons, such that burst firing in relay neurons activates a barrage of EPSPs and a subsequent low threshold Ca2+ spike in PGN cells. This activation of PGN neurons inhibits a substantial number of relay cells, a few of which rebound burst after this IPSP, thus starting the cycle again. Block of GABAA receptors results in a marked enhancement of activity in PGN cells through increased excitation from relay cells and disinhibition from neighbouring PGN cells. This increased activity in PGN neurons results in a markedly enhanced activation of GABAB receptors in relay neurons and the subsequent generation of paroxysmal activity that is similar to that associated with absence seizures.

Animals↗
PubMed1995

Electrophysiological and pharmacological properties of interneurons in the cat dorsal lateral geniculate nucleus.

We investigated the electrophysiological and pharmacological properties of morphologically identified and putative interneurons within laminae A and A1 of the cat dorsal lateral geniculate nucleus maintained in vitro. These intralaminar interneurons possess unique electrophysiological characteristics, including (1) action potentials of a short duration (average width at half amplitude of 0.34 ms). (2) the ability to generate high-frequency trains of action potentials exceeding 500 Hz, without strong spike frequency adaptation, and (3) a low-threshold regenerative response with variable magnitude of expression, ranging from a subthreshold depolarization towards the generation of one to several action potentials in different cells. The low-threshold regenerative depolarization following a hyperpolarizing current pulse was increased in size by application of 4-aminopyridine, was reduced by nickel, and was not influenced by extracellular cesium. These findings indicate that this event is mediated by an underlying Ca(2+)-dependent mechanism, such as a low-threshold Ca(2+) current, that is regulated by the activation of opposing transient K+ currents. Every interneuron tested responded to glutamate, kainate, quisqualate, or N-methyl-D-aspartate with depolarization and action potential discharge. In contrast, we did not observe a postsynaptic response to activation of the metabotropic receptors with 1S,3R-(+/-)-1-amino-cyclopentane-1,3-dicarboxylate. Application of gamma-amino-butyric acid (GABA) strongly inhibited spike firing through a biphasic hyperpolarization and increase in membrane conductance, a response that reversed close to the presumed chloride equilibrium potential and was imitated by the GABAA receptor agonist muscimol. The GABAB receptor agonist baclofen evoked only a weak membrane hyperpolarization from rest and suppression of spontaneous spike activity. Application of acetylcholine, or the muscarinic agonist acetyl-beta-methylcholine, inhibited spontaneous action potential activity through hyperpolarization of the membrane potential, presumably resulting from an increase in membrane potassium conductance. In contrast, application of serotonin only slightly facilitated tonic activity in a subpopulation of interneurons, histamine induced a small slow depolarization apparently through activation of presynaptic excitatory pathways, and noradrenaline and adenosine had no detectable effect on the spontaneous firing or resting potential of interneurons. We suggest that intralaminar interneurons may function in a relatively linear manner to transform retinal and cortical inputs into a local field of inhibition in the dorsal lateral geniculate and that the excitability of these neurons is largely controlled by retinal, cortical, GABAergic, and cholinergic (brainstem) afferents.

Action Potentials↗
PubMed1995

Acetylcholine excites GABAergic neurons of the ferret perigeniculate nucleus through nicotinic receptors.

1. The actions of acetylcholine (ACh) on the GABAergic neurons of the perigeniculate nucleus (PGN) were investigated with the use of extra- and intracellular recording techniques in spontaneously spindling ferret thalamic slices maintained in vitro. 2. Local application of ACh to PGN neurons resulted in rapid depolarization followed by a longer lasting hyperpolarization. Neither of these responses were abolished by blockade of synaptic transmission with tetrodotoxin (TTX) nor with low Ca2+ and elevated Mg2+ solution, indicating that they are direct postsynaptic actions of ACh on PGN cells. Functionally, the rapid depolarizing response could activate both single spike activity, as well as low-threshold Ca2+ spike-mediated bursts. 3. The fast depolarizing response to ACh was selectively blocked by application of the nicotinic antagonist hexamethonium, whereas the slow hyperpolarizing response to ACh was selectively blocked by application of the muscarinic antagonist (-)scopolamine. Application of both hexamethonium and (-)scopolamine blocked the modulation of PGN action-potential firing by ACh. 4. Local application of the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) resulted in a depolarizing response and an increase in membrane conductance, whereas application of the muscarinic agonist DL-muscarine chloride resulted in a hyperpolarizing response and an increase in membrane conductance. When applied to spontaneously spindling PGN cells, both DMPP and DL-muscarine blocked the occurrence of spindle oscillations. However, only DMPP was associated with depolarization and the generation of single spike activity. 5. These results indicate that the GABAergic cells of the PGN possess postsynaptic nicotinic as well as muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1995

Spindle waves are propagating synchronized oscillations in the ferret LGNd in vitro.

1. The cellular features of propagation of spindle waves and a bicuculline-induced slow oscillation through sagittal slices of the ferret dorsal lateral geniculate nucleus (LGNd) maintained in vitro were examined with simultaneous extracellular and intracellular recordings from up to eight sites. Spindle waves typically propagated along the long axis (dorsal-ventral) of the sagittal slice at a speed of 0.3-1.5 mm/s and were synchronized along the line of projection between the perigeniculate nucleus (PGN) and the A, A1, and C laminae. 2. Spindle waves can be initiated with local electrical stimulation or can occur spontaneously in any part of the LGNd/PGN. On initiation of a spindle wave, spindle waves propagate away from the site of initiation. Spindle waves may propagate only locally or may collide with other spindle waves. Collision of spindle waves is associated with synchronization of the two network oscillations, and the spindle waves do not propagate past one another. 3. Repetitive electrical stimulation reveals that spindle wave generation and propagation exhibit a relative refractory period of between 7 and 14 s in vitro. Stimulation at rates of less than the refractory period results in the generation of abbreviated local spindle waves at the stimulation site, but not in the propagation of this spindle wave into adjacent regions of the slice. 4. Local block of non-N-methyl-D-aspartate (non-NMDA) excitatory amino acid receptors in the PGN with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) prevents the propagation of spindle waves across the point of application, indicating that the excitation of PGN neurons by thalamocortical cells is essential to the propagation of these oscillations. The local antagonism of non-NMDA receptors in the PGN results in the dorsal and ventral aspects of the LGNd slice behaving as independent spindle wave generators, even if before application of CNQX they were not. 5. Activation of a burst discharge in a single PGN neuron can result in the generation of a full spindle wave and the propagation of this spindle wave both dorsally and ventrally through the slice away from the activated PGN neuron. The ability of a burst of action potentials in a PGN neuron to generate a spindle wave is suppressed immediately after the generation of a spindle wave, but slowly returns over a 7- to 14-s period corresponding to the relative spindle wave refractory period.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Postnatal development of synchronized network oscillations in the ferret dorsal lateral geniculate and perigeniculate nuclei.

Extracellular and intracellular recordings from slices of ferret dorsal lateral geniculate nucleus (LGNd) at postnatal ages P10-53 were performed to examine the postnatal development of spindle waves and the ability of block of GABAA receptors to alter these spindle waves into a slower, synchronous oscillation. As in prior studies in the adult, intracellular and extracellular recordings at ages P33-53 revealed robust spindle waves to be present in both the LGNd and perigeniculate nucleus (PGN). Intracellular recordings from thalamocortical relay cells in the A-laminae of the LGNd revealed that these cells received repetitive inhibitory postsynaptic potentials (IPSPs) at 6-9 Hz during the generation of spindle waves, and generated rebound low threshold Ca2+ spikes and bursts of 2-6 action potentials following each second or third IPSP. Intracellular recordings from the GABAergic neurons of the PGN at P33-53 revealed barrages of EPSPs that activated low threshold Ca2+ spikes and high frequency burst discharges of 2-10 action potentials during spindle wave generation. In contrast, full spindle waves were absent at ages prior to approximately P22 and spindle waves between the ages of P26 and approximately P30 were relatively weak and associated with only one or two action potentials per burst in both PGN neurons and LGNd relay cells. Bath application of the GABAA antagonist bicuculline methiodide at P41-53 resulted in a conversion of normal spindle waves into a marked 2-4 Hz oscillation in which the action potential firing of both thalamocortical relay and PGN neurons was greatly increased. In contrast, block of GABAA receptors prior to age P39 did not result in the generation of the slowed, 2-4 Hz network oscillation. Investigation of the electrophysiological properties of PGN neurons revealed that the postnatal development of spindle waves and bicuculline-induced slow oscillations were associated with an increase in the ability of PGN neurons to generate high frequency bursts of action potentials, suggesting that these changes in electrophysiological properties may contribute to the late development of synchronized oscillations in the ferret LGNd.

Aging↗
PubMed1994

Sensory gating mechanisms of the thalamus.

The thalamus is an obligatory station through which nearly all sensory information must pass before reaching the cerebral cortex. One of the major functions of the thalamus is the selective control of the flow of sensory-motor information to the cerebral cortex during different states of the sleep-wake cycle and arousal, and is controlled through the actions of various neurotransmitter systems in the brainstem, hypothalamus, and cerebral cortex. Recent investigations have detailed the cellular mechanisms, including the role of GABAA and GABAB receptors, involved in the generation of both normal (e.g. spindle waves) and abnormal (e.g. generalized seizures) patterns of activity in thalamocortical circuits. In addition, in vivo investigations have also revealed that the dense projection from the cerebral cortex to the thalamus may synchronize thalamocortical activity in a manner useful for sensory analysis. Together, these data suggest that oscillations and synchronization are important for both normal and abnormal function in thalamocortical circuits.

Animals↗
PubMed1994

Enhanced activation of NMDA receptor responses at the immature retinogeniculate synapse.

The maturation of retinogeniculate excitatory transmission and intrathalamic inhibition was studied in slices of the dorsal LGN obtained from ferrets during the first 2 postnatal months. Response to optic tract stimulation at neonatal ages consisted of slow EPSPs lasting several hundred milliseconds. Application of the NMDA receptor antagonist D-(-)-2-amino-5-phosphonovaleric acid (D-APV) during the first 2 postnatal weeks resulted in EPSPs that were reduced in peak amplitude and dramatically curtailed in duration, indicating that NMDA receptors participate strongly in retinogeniculate transmission at the immature synapse. Gradually, EPSPs became shorter in duration such that after the second postnatal week, the retinogeniculate EPSPs were only a few milliseconds in duration. At this late stage of development responses were remarkably less affected by application of D-APV. These changes in contribution of NMDA receptors to retinogeniculate transmission were found to be due to the development of strong IPSPs, the result of gradual maturation of activation of GABAergic inhibition. Indeed, application of bicuculline methiodide to block GABAA receptor-mediated IPSPs strongly enhanced the NMDA component of the EPSPs in more mature cells. The voltage dependence and kinetics of NMDA-induced excitatory postsynaptic currents (NMDA EPSCs) were characterized by voltage-clamp recordings after blocking AMPA/kainate receptors with 6-cyano-7-nitroquinoxaline-2,3-dione and GABAA receptors wit' bicuculline methiodide. The voltage dependence of the NMDA EPSCs remained unaltered with age. During the first postnatal month the kinetic properties of the NMDA EPSCs also remained unaltered, but a reduction in EPSC duration was observed within the following weeks, well after the critical period of anatomical reorganization.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1994

Developmental changes in electrophysiological properties of LGNd neurons during reorganization of retinogeniculate connections.

Changes in electrophysiological properties of neurons in the ferret dorsal LGN (LGNd) were studied during early postnatal life, a critical developmental period when changes occur in morphology, connectivity, and response properties of LGNd neurons. Using the patch-clamp technique to obtain whole-cell recordings from cells maintained as in vitro slices of thalamus, several distinctive properties were observed in the immature LGNd. Relatively low resting membrane potentials were present that became more negative during the first 2 postnatal weeks. In addition, immature neurons exhibited high input resistances that decreased during early postnatal development. At all ages postnatally, neurons were capable of generating a train of Na(+)-dependent action potentials in response to intracellular injection of a depolarizing current pulse. Moreover, immature neurons resembled older cells in that little spike frequency adaptation was present during a train of action potentials. Action potential activity in immature neurons was nevertheless distinctive in several respects: (1) during the first 2-3 postnatal weeks action potentials became shorter in duration and larger in amplitude; (2) during the same period, thresholds for generation of action potentials changed in conjunction with the changes in resting membrane potential, becoming more negative; and (3) plots of frequency versus injected current revealed that thresholds for generation of trains of action potentials were reached with intracellular injection of lower current levels at earlier ages. These findings raise the possibility that relatively weak ionic currents generated at immature synapses have unexpectedly strong effects on the young LGNd neuron.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Thalamocortical oscillations in the sleeping and aroused brain.

Sleep is characterized by synchronized events in billions of synaptically coupled neurons in thalamocortical systems. The activation of a series of neuromodulatory transmitter systems during awakening blocks low-frequency oscillations, induces fast rhythms, and allows the brain to recover full responsiveness. Analysis of cortical and thalamic networks at many levels, from molecules to single neurons to large neuronal assemblies, with a variety of techniques, ranging from intracellular recordings in vivo and in vitro to computer simulations, is beginning to yield insights into the mechanisms of the generation, modulation, and function of brain oscillations.

Animals↗
PubMed1993

Cellular mechanisms of a synchronized oscillation in the thalamus.

Spindle waves are a prototypical example of synchronized oscillations, a common feature of neuronal activity in thalamic and cortical systems in sleeping and waking animals. Spontaneous spindle waves recorded from slices of the ferret lateral geniculate nucleus were generated by rebound burst firing in relay cells. This rebound burst firing resulted from inhibitory postsynaptic potentials arriving from the perigeniculate nucleus, the cells of which were activated by burst firing in relay neurons. Reduction of gamma-aminobutyric acidA (GABAA) receptor-mediated inhibition markedly enhanced GABAB inhibitory postsynaptic potentials in relay cells and subsequently generated a slowed and rhythmic population activity resembling that which occurs during an absence seizure. Pharmacological block of GABAB receptors abolished this seizure-like activity but not normal spindle waves, suggesting that GABAB antagonists may be useful in the treatment of absence seizures.

Animals↗
PubMed1993

A model for 8-10 Hz spindling in interconnected thalamic relay and reticularis neurons.

We investigated a simplified model of a thalamocortical cell and a reticular thalamic cell interconnected with excitatory and inhibitory synapses, based on Hodgkin-Huxley type kinetics. The intrinsic oscillatory properties of the model cells were similar to those observed from single cells in vitro. When synaptic interactions were included, spindle oscillations were observed consisting of sequences of rhythmic oscillations at 8-10 Hz separated by silent periods of 8-40 s. The model suggests that Ca2+ regulation of lh channels may be responsible for the waxing and waning of spindles and that the reticular cell shapes the 10-Hz rhythmicity. The model also predicts that the kinetics of gamma-aminobutyric acid inhibitory postsynaptic potentials as well as the intrinsic properties of reticular cells are critical in determining the frequency of spindle rhythmicity.

Animals↗
PubMed1993

Mechanisms of oscillatory activity in guinea-pig nucleus reticularis thalami in vitro: a mammalian pacemaker.

1. The ionic mechanisms of rhythmic burst firing and single spike, tonic discharge were investigated with extracellular and intracellular recordings of single neurones in the guinea-pig nucleus reticularis thalami (NRT) maintained as a slice in vitro. 2. Activation of cortical/thalamic afferents to NRT neurones resulted in a short latency burst of action potentials which could be followed by a rhythmic sequence of oscillatory burst firing. Intracellularly, this oscillatory activity was associated with an alternating sequence of low threshold Ca2+ spikes separated by after-hyperpolarizing potentials. Intracellular injection of short duration hyperpolarizing current pulses resulted in a similar sequence of oscillatory burst firing, suggesting that this activity is an intrinsic property of NRT cells. The frequency of rhythmic burst firing was highly voltage and temperature dependent and was between 7-12 Hz at -65 to -60 mV at 38 degrees C. In addition, at depolarized membrane potentials, oscillatory burst firing was typically followed by a prolonged tail of single spike activity. 3. Application of the Na+ channel poison tetrodotoxin blocked the generation of fast action potentials, but left intact the rhythmic sequence of low threshold Ca2+ spikes separated by after-hyperpolarizing potentials (AHPs). The reversal potential of the AHPs was -94 mV, suggesting that it was mediated by an increase in K+ conductance. Extracellular application of tetraethylammonium or apamin, or intracellular injection of Cs+ or the Ca2+ chelating agent EGTA, blocked the Ca2+ spike AHP, indicating that it is mediated by a Ca(2+)-activated K+ current. 4. Block of the AHP resulted in the marked enhancement of a slow after-depolarizing potential (ADP). The slow ADP occurred only following the generation of low threshold Ca2+ spikes. Replacement of extracellular Ca2+ with Mg2+ or Sr2+ resulted in an abolition of the slow ADP. In addition, the increase in [Mg2+]o resulted in an abolition of the low threshold Ca2+ spike. In contrast, replacement of extracellular Ca2+ with Ba2+ did not abolish the slow ADP. These results indicate that the ADP can be activated by either Ca2+ or Ba2+, but not by Mg2+ or Sr2+. 5. Replacement of extracellular Na+ with choline+ did not abolish the slow ADP, while replacement with N-methyl-D-glucamine+ did, indicating that the slow ADP can be supported by choline+, but not by N-methyl-D-glucamine+. Neither chemical affected the low threshold Ca2+ spike. These results are consistent with the slow ADP being mediated by a Ca(2+)-activated non-selective cation (CAN) current.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1993

Control of firing mode of corticotectal and corticopontine layer V burst-generating neurons by norepinephrine, acetylcholine, and 1S,3R-ACPD.

The ionic mechanisms by which the firing mode of layer V burst-generating neurons is modulated by noradrenergic, cholinergic, and glutamate metabotropic receptors were investigated with intracellular and extracellular recordings obtained in slices of guinea pig sensorimotor and primary visual cortices maintained in vitro. Extracellular and intracellular recordings revealed that a subset of layer V cells spontaneously generated bursts of three to six action potentials with an interburst frequency of 0.2-4 Hz. Depolarization of these cells with the intracellular injection of current inhibited burst firing and switched the cells to the tonic, single-spike mode of action potential generation. Intracellular recording from retrogradely labeled layer V pyramidal cells that project to either the superior colliculus or pontine nuclei revealed that a substantial portion of these are burst-generating cells. Application of norepinephrine (NE), the glutamate metabotropic receptor agonist 1S,3R-aminocyclopentane-1,3-dicarboxylic acid (ACPD), or ACh to layer V burst-generating cells resulted in depolarization and a subsequent shift in firing pattern from spontaneously bursting to single-spike activity. Pharmacological analysis of these responses indicated that they are mediated by the alpha 1-adrenoceptor for NE and the muscarinic subtype for ACh. Thus, the NE response was mimicked by the alpha-agonist phenylephrine but not by the beta-agonist isoprenaline, and was completely blocked by the alpha 1-antagonist prazosin but not by the alpha 2-antagonist yohimbine or the beta-antagonist propranolol. Finally, the ACh effect could be mimicked by the muscarinic agonist acetyl-beta-methylcholine (MCh) and was blocked by the muscarinic antagonist scopolamine. Intracellular recordings revealed that the NE-, MCh-, and ACPD-induced responses in bursting neurons are due to the direct activation of receptors on these cells, since block of synaptic transmission with local application of TTX or bath application of low [Ca2+]o and raised [Mg2+]o did not block the postsynaptic responses. Voltage-clamp analysis of the currents involved in the depolarizing responses of bursting cells revealed that activation of alpha 1-adrenergic, muscarinic, or glutamate metabotropic receptors resulted in a decrease in a potassium conductance that consisted of both a voltage-independent component and a voltage- and Ca(2+)-sensitive component. These results suggest that increased activity in noradrenergic, cholinergic, and glutamatergic pathways may control the firing mode of layer V corticotectal and corticopontine pyramidal cells by determining the resting membrane potential through modulation of both voltage-dependent and voltage-independent K+ conductances.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1992

Corticothalamic activation modulates thalamic firing through glutamate "metabotropic" receptors.

The mammalian thalamus forms an obligatory relay for nearly all sensory information that reaches the cerebral cortex. The transmission of sensory information by the thalamus varies in a state-dependent manner, such that during slow wave sleep or drowsiness thalamic responsiveness is markedly reduced, whereas during the waking, attentive state transmission is enhanced. Although activation of brainstem inputs to thalamic neurons has long been assumed to underlie this gating of sensory transfer through the thalamus, numerically the largest input to thalamic relay neurons derives from layer VI cells of the cerebral cortex. Here we report that activation of corticothalamic fibers causes a prolonged excitatory postsynaptic potential in guinea pig dorsal lateral geniculate relay neurons resulting from the reduction of a potassium conductance, consistent with the activation of glutamatergic "metabotropic" receptors. This slow depolarization can switch firing of thalamic neurons from the burst firing mode, which is prevalent during slow wave sleep, to the single spike mode, which is prevalent during waking, thereby facilitating transmission of sensory information through the thalamus. This prolonged enhancement of thalamic transfer may allow the cerebral cortex to gate or control selective fields of sensory inputs in a manner that facilitates arousal, attention, and cognition.

Action Potentials↗
PubMed1992

Neurotransmitter actions in the thalamus and cerebral cortex.

The postsynaptic actions of glutamate, gamma-aminobutyric acid (GABA), acetylcholine, norepinephrine, serotonin, and histamine in the cerebral cortex and thalamus and their relevance to the control of thalamocortical activity are reviewed. Excitatory and inhibitory amino acids (such as glutamate and GABA) are proposed to form the neurotransmitters by which the executative neural networks of the neocortex and thalamus process synaptic information. In contrast, the more slowly acting neurotransmitters, acetylcholine, norepinephrine, serotonin, and histamine, are proposed to control the state of activity and excitability of thalamic and cortical neurons and thereby modulate the state of thalamocortical activity. Specific examples of the involvement of fast and slow transmitter actions in the genesis of epileptic seizures and the determination of sleep-wake cycles are given.

Animals↗
PubMed1992

Simulation of the currents involved in rhythmic oscillations in thalamic relay neurons.

1. To perform simulations of the various modes of action potential generation in thalamic relay neurons, we developed Hodgkin-and-Huxley style mathematical equations that describe the voltage dependence and kinetics of activation and inactivation of four different currents, including the transient, low-voltage-activated Ca2+ current (IT), the rapidly inactivating transient K+ current (IA), the slowly inactivating K+ current (IK2), and the hyperpolarization-activated, mixed cationic current (Ih). The modeled currents were derived either from acutely dissociated rat thalamic relay neurons (IT, IA, IK2), or from guinea pig thalamic relay cells maintained in slices in vitro (Ih). 2. The voltage dependence of steady-state activation and inactivation of IT, IA, and IK2 and the activation of Ih could be modeled with Boltzmann-style equations. Modeling of the behavior of IT to depolarizing steps in voltage clamp required the use of the constant field equation to relate permeability to T-current amplitude. The time constant of activation of IT was described by a continuous bell-shaped function with a maximum near 15 ms at threshold for activation (-75 mV) and 23 degrees C. Mathematical description of the kinetics of inactivation and removal of inactivation of this current required two separate functions. 3. The rapidly activating and inactivating K+ current IA was modeled by assuming two components with different time constants of inactivation. The kinetics of activation was described as a continuous function of voltage with the slowest time constant, near 2.5 ms, at threshold for activation (-60 mV) and 23 degrees C. In contrast, the kinetics of inactivation of both components were described as voltage independent, consistent with experimental data. The rate or removal of inactivation of both components of IA was described as continuously increasing with the degree of hyperpolarization. 4. The slowly inactivating K+ current IK2 was also modeled by assuming two components with different rates of inactivation. The kinetics of activation were described by a bell-shaped function with a maximum time constant near 80 ms at -40 mV and 23 degrees C, whereas threshold for activation was approximately -60 mV. Inactivation of both components was modeled as relatively independent of voltage, whereas removal of inactivation was described as a continuous function of membrane potential. 5. The hyperpolarization-activation cationic current, Ih, was modeled by assuming that the current activates with a single exponential relation and does not inactivate.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗