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D A McCormick

Publications and source records attributed to D A McCormick.

At least 73 records · Page 4Linked to original sources
PubMed1992

A model of the electrophysiological properties of thalamocortical relay neurons.

1. A model of the electrophysiological properties of single thalamocortical relay neurons in the rodent and cat dorsal lateral geniculate nucleus was constructed, based in part on the voltage dependence and kinetics of ionic currents detailed with voltage-clamp techniques. The model made the simplifying assumption of a single uniform compartment and incorporated a fast and transient Na+ current, INa; a persistent, depolarization-activated Na+ current, INap; a low-threshold Ca2+ current, I(T); a high-threshold Ca2+ current, IL; a Ca(2+)-activated K+ current, IC; a transient and depolarization-activated K+ current, IA; a slowly inactivating and depolarization-activated K+ current, IK2; a hyperpolarization-activated cation current, Ih; and K+ and Na+ leak currents IKleak and INaleak. 2. The effects of the various ionic currents on the electrophysiological properties of thalamocortical relay neurons were initially investigated through examining the effect of each current individually on passive membrane responses. The two leak currents, IKleak and INaleak, determined in large part the resting membrane potential and the apparent input resistance of the model neuron. Addition of IA resulted in a delay in the response of the model cell to a depolarizing current pulse, whereas addition of IK2, or IL combined with IC, resulted in a marked and prolonged decrease in the response to depolarization. Addition of Ih resulted in a depolarizing "sag" in response to hyperpolarization, whereas addition of IT resulted in a large rebound Ca2+ spike after hyperpolarization. Finally, addition of INap resulted in enhancement of depolarization. 3. The low-threshold Ca2+ spike of rodent neurons was successfully modeled with the active currents I(T), IL, IA, IC, and IK2. The low-threshold Ca2+ current I(T) generated the low-threshold Ca2+ spike. The transient K+ current IA slowed the rate of rise and reduced the peak amplitude of the low-threshold Ca2+ spike, whereas the slowly inactivating K+ current IK2 contributed greatly to the repolarization of the Ca2+ spike. Activation of IL during the peak of the Ca2+ spike led to activation of IC, which also contributed to the repolarization of the Ca2+ spike. Reduction of any one of the K+ currents resulted in an increase in the other two, thereby resulting in substantially smaller changes in the Ca2+ spike than would be expected on the basis of the amplitude of each ionic current alone.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1992

Cellular mechanisms underlying cholinergic and noradrenergic modulation of neuronal firing mode in the cat and guinea pig dorsal lateral geniculate nucleus.

The functional properties, ionic basis, and possible convergence and interaction of postsynaptic actions mediated by muscarinic and alpha 1-adrenergic receptors were examined in cat and guinea pig dorsal lateral geniculate (LGNd) neurons maintained in thalamic slices in vitro. The possible involvement of GTP-binding proteins was also examined. Extracellular recordings from cat LGNd revealed the presence of two subpopulations of neurons. The most prevalent generated rhythmic high-frequency (300-500 Hz) bursts of two to six action potentials each, with an interburst frequency of 1-3 Hz. Intracellular recordings revealed that this activity is typical of thalamocortical relay cells in the apparent absence of neuromodulatory input. Application of ACh or noradrenaline (NA) to rhythmically oscillating neurons in the cat LGNd resulted in cessation of this activity followed by the appearance of single spike firing. Intracellular recordings revealed that this change in firing mode was associated with a depolarization of the neuron out of the range of intrinsic rhythmic oscillation and into or near the single spike firing mode. The voltage characteristics of the current underlying the cholinergic and noradrenergic slow depolarization were investigated in guinea pig LGNd neurons. Application of the muscarinic agonist acetyl-beta-methylcholine (MCh) to presumed relay neurons resulted in a hyperpolarization due to the activation of an outward K+ current. This response was followed by a slow depolarization due to reduction of a relatively non-voltage-dependent potassium current distinct from IM and IAHP. Application of NA resulted in a slow depolarization that was also associated with reduction of this relatively linear K+ current. The MCh- and NA-induced slow depolarizations displayed the property of occlusion, indicating convergence of action. However, these responses were mediated by pharmacologically distinct receptors since the MCh-induced reduction in K+ current was blocked by scopolamine while that induced by NA was blocked by the alpha 1-adrenoceptor antagonist prazosin. Intracellular diffusion of GTP-gamma-S resulted in the inward current responses to NA and MCh being irreversible, suggesting the possible involvement of a G-protein. Prior exposure to pertussis toxin did not affect the inward current response to NA and MCh, while the outward K+ current responses induced by application of MCh or the GABAB agonist baclofen were blocked. These results reveal that activation of muscarinic or alpha 1-adrenergic postsynaptic receptors in the LGNd result in a shift in firing mode from rhythmic oscillation to tonic single spike activity through a decrease in a relatively linear K+ current mediated through a pertussis toxin-insensitive G-protein.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1991

Actions of norepinephrine in the cerebral cortex and thalamus: implications for function of the central noradrenergic system.

Norepinephrine (NE) has potent and long-lasting ionic effects on cortical and thalamic neurons. In cortical pyramidal cells, activation of beta-adrenergic receptors results in an enhanced excitability and responsiveness to depolarizing inputs. This enhanced excitability is expressed as a reduction in spike frequency adaptation and is mediated by a marked suppression of a slow Ca(++)-activated potassium current known as IAHP. In the thalamus, application of NE results in the suppression of ongoing rhythmic burst activity and a switch to the single spike firing mode of action potential generation. This effect is mediated through an alpha 1-adrenergic suppression of a resting leak potassium current, IKL, and through a beta-adrenoceptor-mediated enhancement of the hyperpolarization activated cation current Ih. Together with the actions of other neuromodulatory neurotransmitters (i.e., acetylcholine, histamine, serotonin) these effects facilitate the switch of these neurons from a state of rhythmic oscillation and low excitability during drowsiness and slow-wave sleep to a state of increased excitability and responsiveness during periods of waking, attentiveness and cognition.

Action Potentials↗
PubMed1991

Serotonin and noradrenaline excite GABAergic neurones of the guinea-pig and cat nucleus reticularis thalami.

1. The actions of serotonin (5-HT) and noradrenaline (NA) in the cat perigeniculate nucleus (PGN) and the guinea-pig nucleus reticularis thalami (NRT) were investigated with extracellular and intracellular recordings obtained from neurones in thalamic slices maintained in vitro. 2. Single, local application of either 5-HT or NA resulted in pronounced (5-50 Hz) and prolonged (2-10 min) excitation associated with the occurrence of single-spike activity. Serotoninergic excitation was specifically blocked by the 5-HT2/5-HT1C antagonists ketanserin and ritanserin, but not by the 5-HT1A antagonist pindolol or the 5-HT3 antagonist ICS 205-930. Furthermore, the 5-HT response was mimicked by alpha-methyl-5-HT, but not by the 5-HT1A agonist 8-hydroxydipropylaminotetralin (8-OHDPAT) or the 5-HT3 agonist 2-methyl-5-HT. Together, these results indicate that this excitatory response is mediated through 5-HT2 receptors with the possible involvement of 5-HT1C receptors. 3. Noradrenergic excitation was specifically blocked by the alpha 1-antagonist prazosin, but not by the beta-antagonist propranolol or the alpha 2-antagonist yohimbine. Similarly, the response was mimicked by the alpha-agonist phenylephrine, but not by the beta-agonist isoprenaline. These results indicate that the noradrenergic excitation is mediated by alpha 1-adrenoceptors. 4. Block of synaptic transmission either by lowering external calcium concentration ([Ca2+]o) to 0.5 mM and raising external magnesium concentration ([Mg2+]o) to 10 mM or by local application of tetrodotoxin failed to block the excitatory or depolarizing response to 5-HT or NA indicating that these responses are direct and not mediated through the release of other neurotransmitters. 5. Intracellular recordings revealed that the 5-HT- and NA-induced excitations are mediated by a pronounced slow depolarization associated with an apparent decrease in input conductance and an increase in the membrane time constant. Current versus voltage plots obtained under voltage clamp before and during the presence of 5-HT and NA revealed that these neurotransmitters induced an inward current which reversed to an outward current at -107 and -110 mV, respectively, in 2.5 mM external potassium concentration ([K+]o). This reversal potential was identical to that associated with an increase in potassium conductance activated by acetylcholine (-110 mV) in the same neurones. Plots of the amplitude of the 5-HT- or NA-induced current versus membrane potential revealed a linear relationship in the voltage range from -140 to -60 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1991

Functional properties of a slowly inactivating potassium current in guinea pig dorsal lateral geniculate relay neurons.

1. The time- and voltage-dependent properties of a slowly inactivating and depolarization-activated potassium current and the functional consequences of its activation was investigated with current and single-electrode voltage-clamp techniques applied to guinea pig dorsal lateral geniculate neurons maintained as a slice in vitro. 2. In current clamp, application of a step depolarization to near firing threshold resulted in a slowly rising membrane potential that took up to 10 s to reach steady state and firing threshold. In voltage clamp, step depolarization of the membrane potential to values positive to approximately -65 mV resulted in the rapid activation followed by slow inactivation of an outward current. In both cases the sudden depolarization was associated with a large increase in membrane conductance, which gradually lessened in parallel with the slow depolarization in current clamp or with the decrease in outward current in voltage clamp. 3. The time course of inactivation of the outward current, which we refer to as IAs, was well fitted by a two-exponential function with time constants of 96 and 2,255 ms, suggesting the presence of a fast and slow phase of inactivation. The activation threshold for IAs was about -65 to -60 mV, whereas inactivation was incomplete even at -50 mV, suggesting the presence of a substantial "window" current. The time course of removal of inactivation of IAs at -85 to -100 mV was well fitted by a single exponential function with time constant of 91 ms. 4. IAs appears to be mediated by K+. Increasing [K+]o from 2.5 to 10 mM resulted in a reduction in amplitude of IAs, whereas changing from 10 to 2.5 mM [K+]o enhanced this current. Intracellular injection of Cs+ resulted in an abolition of IAs, whereas extracellular application of Ba2+ resulted in a large decrease in the apparent input conductance but relatively little reduction of IAs. 5. Both phases of inactivation of the transient outward current were completely blocked by low doses (100 microM) of 4-aminopyridine (4-AP), but not by extracellular application of Cs+, tetraethylammonium (TEA), tetrodotoxin (TTX), or after block of transmembrane Ca2+ currents. Local application of 4-AP to neurons depolarized to near firing threshold resulted in depolarization associated with a decrease in apparent input conductance, thereby confirming the presence of a window current.4+ this bias against depolarizing inputs.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗
PubMed1991

Modulation of neuronal firing mode in cat and guinea pig LGNd by histamine: possible cellular mechanisms of histaminergic control of arousal.

The thalamus is innervated by histaminergic fibers presumably arising from neurons in the tuberomammillary nucleus of the hypothalamus. The possible function of this histaminergic projection was addressed through investigation of the cellular actions of histamine on guinea pig and cat dorsal lateral geniculate (LGNd) relay neurons maintained as a slice in vitro. Local application of histamine to LGNd relay neurons resulted in a slow depolarization that was associated with a decrease in membrane conductance and was blocked by the H1-antagonists pyrilamine, triprolidine, or diphenhydramine. Current versus voltage relationships revealed that the slow depolarization was associated with an inward current that reversed near EK, indicating that it was due to a decrease in a potassium current. The slow depolarizing response to histamine was occluded by maximal activation of the slow depolarizing responses resulting from stimulation of alpha 1-adrenergic or muscarinic receptors, suggesting that they are all mediated by reduction in the same potassium current and/or alteration of a common second messenger. In the presence of H1-receptor antagonists, application of histamine resulted in a small depolarization that was associated with a marked increase in apparent membrane conductance. Voltage-clamp recordings revealed that this response was associated with enhancement of the hyperpolarization-activated cation current Ih. This response to histamine was blocked by local or bath application of the H2-antagonists cimetidine or tiotidine. The functional consequences of these actions of histamine were addressed with extracellular and intracellular recordings in guinea pig and cat LGNd relay neurons. Extracellular recordings in cat LGNd revealed the occurrence of highly regular 1-4 Hz rhythmic burst discharges. Application of histamine halted rhythmic bursting and replaced it with a prolonged period of single-spike activity. Intracellular recordings indicate that the histamine-induced switch in firing mode is due largely to the slow depolarizing response mediated by H1-receptors, but is also facilitated by the enhancement of Ih mediated by H2-receptors. These postsynaptic actions indicate that increased activity in the tuberomammillary histaminergic system may result in a switch of thalamic neuronal activity from rhythmic burst firing to single-spike activity and thereby promote the accurate transmission and processing of sensory information and cognition.

Acetylcholine↗
PubMed1990

Functional implications of burst firing and single spike activity in lateral geniculate relay neurons.

Guinea-pig thalamocortical relay neurons can intrinsically generate action potentials in two distinct patterns: as high frequency bursts or as relatively independent single spikes. The burst firing mode is due to the presence of a low threshold Ca2+ current and imposes a marked non-linear transformation on depolarizing or hyperpolarizing inputs. In the burst firing mode, thalamic neurons respond to increasing frequencies of depolarizing inputs with progressively fewer action potentials such that they fail to respond to inputs arriving at rates greater than approximately 15 Hz. In this manner, the amplitude of the burst discharge relays little information concerning the characteristics of phasic excitatory postsynaptic potentials which may trigger them, but rather is determined by the membrane potential preceding the burst and the time interval since the last burst. In contrast to the behavior of neurons in the burst firing mode, the pattern of action potentials generated after depolarization into the single spike mode is a more faithful representation of the characteristics of incoming excitatory postsynaptic potentials or depolarizing inputs. The pattern of action potentials generated in the single spike mode is determined by the intensity, duration, and frequency of incoming excitatory inputs even when they arrive at rates in excess of 100 Hz. These, and other properties, allow thalamic neurons to possess two distinct states of neuronal activity: an oscillatory mode in which rhythmic bursts of action potentials are generated and in which responsiveness to stimulation of peripheral receptive fields is greatly reduced, and a transfer mode in which action potentials are generated in relative independence of one another and in which the ability to respond to barrages of phasic excitatory inputs is greatly enhanced. The presence of the rhythmic burst firing mode may therefore facilitate the filtering of sensory information during periods of drowsiness, inattentiveness, and slow wave sleep.

Animals↗
PubMed1990

Properties of a hyperpolarization-activated cation current and its role in rhythmic oscillation in thalamic relay neurones.

1. The physiological and functional features of time-dependent anomalous rectification activated by hyperpolarization and the current which underlies it, Ih, were examined in guinea-pig and cat thalamocortical relay neurones using in vitro intracellular recording techniques in thalamic slices. 2. Hyperpolarization of the membrane from rest with a constant-current pulse resulted in time-dependent rectification, expressed as a depolarizing sag of the membrane potential back towards rest. Under voltage clamp conditions, hyperpolarizing steps to membrane potentials negative to approximately -60 mV were associated with the activation of a slow inward current, Ih, which showed no inactivation with time. 3. The activation curve of the conductance underlying Ih was obtained through analysis of tail currents and ranged from -60 to -90 mV, with half-activation occurring at -75 mV. The time course of activation of Ih was well fitted by a single-exponential function and was strongly voltage dependent, with time constants ranging from greater than 1-2 s at threshold to an average of 229 ms at -95 mV. The time course of de-activation was also described by a single-exponential function, was voltage dependent, and the time constant ranged from an average of 1000 ms at -80 mV to 347 ms at -55 mV. 4. Raising [K+]o from 2.5 to 7.5 mM enhanced, while decreasing [Na+]o from 153 to 26 mM reduced, the amplitude of Ih. In addition, reduction of [Na+]o slowed the rate of Ih activation. These results indicate that Ih is carried by both Na+ and K+ ions, which is consistent with the extrapolated reversal potential of -43 mV. Replacement of Cl- in the bathing medium with isethionate shifted the chloride equilibrium potential positive by approximately 30-70 mV, evoked an inward shift of the holding current at -50 mV, and resulted in a marked reduction of instantaneous currents as well as Ih, suggesting a non-specific blocking action of impermeable anions. 5. Local (2-10 mM in micropipette) or bath (1-2 mM) applications of Cs+ abolished Ih over the whole voltage range tested (-60 to -110 mV), with no consistent effects on instantaneous currents. Barium (1 mM, local; 0.3-0.5 mM, bath) evoked a steady inward current, reduced the amplitude of instantaneous currents, and had only weak suppressive effects on Ih. 6. Block of Ih with local application of Cs+ resulted in a hyperpolarization of the membrane from the resting level, a decrease in apparent membrane conductance, and a block of the slow after-hyperpolarization that appears upon termination of depolarizing membrane responses, indicating that Ih contributes substantially to the resting and active membrane properties of thalamocortical relay neurones.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1990

Noradrenergic and serotonergic modulation of a hyperpolarization-activated cation current in thalamic relay neurones.

1. Modulation of the hyperpolarization-activated cation current, Ih, by noradrenaline (NA) and serotonin (5-HT) was examined in guinea-pig and cat medial and lateral geniculate relay neurones using the in vitro slice technique. 2. In the absence of pharmacological antagonists, local application of NA resulted in a slow depolarization and decrease in apparent input conductance, a response which was blocked by local or bath application of the alpha 1-adrenoceptor antagonist prazosin. Application of NA after pharmacological block of alpha 1- and alpha 2-adrenoceptors, or application of 5-HT in all conditions, induced a 1-3 mV slow depolarization which was associated with a pronounced increase in apparent input conductance. This response to NA and 5-HT persisted during blocked synaptic transmission and was present in both the guinea-pig and cat medial and lateral geniculate nuclei. 3. The increase in membrane conductance elicited by NA was mimicked by the beta-specific agonist isoprenaline and blocked by the beta-antagonists propranolol and atenolol, indicating that it is mediated by beta-adrenoceptors. The response to 5-HT was blocked by the 5-HT1 and 5-HT2 antagonist methysergide, but not by the 5-HT2 antagonist ritanserin. Applications of either the 5-HT1A agonist ipsapirone or the partial agonist 8-hydroxy-dipropylaminotetralin (8-OHDPAT) were without effect. 4. Current versus voltage relationships obtained under voltage clamp revealed NA and 5-HT to cause a voltage-dependent inward shift at membrane potentials negative to approximately -60 mV. This response appeared to be shared by NA and 5-HT since maximal application of 5-HT greatly reduced or abolished the response to NA. 5. Application of NA and/or 5-HT during hyperpolarizing voltage steps in voltage clamp resulted in a marked increase in amplitude of the hyperpolarization-activated cation current, Ih. In addition, the rate of activation of Ih was strongly increased during activation of beta-adrenoceptors. 6. The activation curve of the conductance underlying Ih (Gh) was shifted by 4-6 mV on the voltage axis with NA and/or 5-HT. The positive shift of Gh activation in the voltage domain resulted in an increase in the amplitude of Gh which is active at resting, and more hyperpolarized, membrane potentials. The subsequent increase in resting membrane conductance decreased the responsiveness of thalamic neurones to hyperpolarizations of all durations. 7. Local or bath application of caesium blocked both Ih and the increase in membrane conductance in response to NA and 5-HT. By contrast, barium blocked neither Ih nor the responses to NA and 5-HT.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1990

Mucin depletion in inflammatory bowel disease.

The mucin and gland content of 26 rectal biopsy specimens--five normal specimens, 10 from patients with ulcerative colitis, and 11 from patients with Crohn's disease--were measured using a Quantimet image analyser. There was significantly less mucin in the groups with ulcerative colitis compared with either those with Crohn's disease or the normal controls. The difference in the gland content between the groups with ulcerative colitis and Crohn's disease and between the group with Crohn's disease and the normal controls did not reach significance. The results suggest that it is worth while assessing the mucin content of rectal biopsy specimens from patients with inflammatory bowel disease. In routine practice this assessment can be made by eye using a suitably stained section.

Colitis, Ulcerative↗
PubMed1989

Noradrenaline and serotonin selectively modulate thalamic burst firing by enhancing a hyperpolarization-activated cation current.

Neurons in many regions of the mammalian nervous system generate action potentials in two distinct modes: rhythmic oscillations in which spikes cluster together in a cyclical manner, and single spike firing in which action potentials occur relatively independently of one another. Which mode of action potential generation a neuron displays often varies with the behavioural state of the animal. For example, the shift from slow-wave sleep to waking and attentiveness is associated with a change in thalamic neurons from rhythmic burst firing to repetitive single spike activity, and a greatly increased responsiveness to excitatory synaptic inputs. This marked change in firing pattern and excitability is controlled in part by ascending noradrenergic and serotonergic inputs from the brainstem, although the cellular mechanisms of this effect have remained largely unknown. Here we report that noradrenaline and serotonin enhance a mixed Na+/K+ current which is activated by hyperpolarization (Ih) and that this enhancement may be mediated by increases in intracellular concentration of cyclic AMP. This novel action of noradrenaline and serotonin reduces the ability of thalamic neurons to generate rhythmic burst firing and promotes a state of excitability that is conducive to the thalamocortical synaptic processing associated with cognition.

Action Potentials↗
PubMed1989

Cholinergic and noradrenergic modulation of thalamocortical processing.

During periods of drowsiness and synchronized sleep, thalamocortical neuronal activity is dominated by rhythmic oscillations. The shift to waking and attentiveness is associated with an abolition of these rhythms and a marked increase in neuronal responsiveness to synaptic inputs. These shifts in thalamocortical processing are controlled by ascending modulatory neurotransmitter systems of which the cholinergic and noradrenergic components play a key role. By altering the amplitude of specialized potassium currents in thalamic and cortical neurons, acetylcholine and norepinephrine can block the generation of thalamocortical rhythms and promote a state of excitability that is consistent with cognition.

Adrenergic Fibers↗
PubMed1989

Convergence and divergence of neurotransmitter action in human cerebral cortex.

The postsynaptic actions of acetylcholine, adenosine, gamma-aminobutyric acid, histamine, norepinephrine, and serotonin were analyzed in human cortical pyramidal cells maintained in vitro. The actions of these six putative neurotransmitters converged onto three distinct potassium currents. Application of acetylcholine, histamine, norepinephrine, or serotonin all increased spiking by reducing spike-frequency adaptation, in part by reducing the current that underlies the slow after hyperpolarization. In addition, application of muscarinic receptor agonists to all neurons or of serotonin to middle-layer cells substantially reduced or blocked the M-current (a K+ current that is voltage and time dependent). Inhibition of neuronal firing was elicited by adenosine, baclofen (a gamma-aminobutyric acid type B receptor agonist), or serotonin and appeared to be due to an increase in the same potassium current by all three agents. These data reveal that individual neuronal currents in the human cerebral cortex are under the control of several putative neurotransmitters and that each neurotransmitter may exhibit more than one postsynaptic action. The specific anatomical connections of these various neurotransmitter systems, as well as their heterogeneous distribution of postsynaptic receptors and responses, allows each to make a specific contribution to the modulation of cortical activity.

Adenosine↗
PubMed1989

GABA as an inhibitory neurotransmitter in human cerebral cortex.

1. The possible role of gamma-aminobutyric acid (GABA) as an inhibitory neurotransmitter in the human cerebral cortex was investigated with the use of intracellular recordings from neocortical slices maintained in vitro. 2. Electrical stimulation of afferents to presumed pyramidal cells resulted in an initial excitatory postsynaptic potential (EPSP) followed by fast and slow inhibitory postsynaptic potentials (IPSPs). The early IPSP had an average reversal potential of -68 mV, was associated with a mean 67-nS increase in membrane conductance, was reduced by the GABAA antagonist bicuculline, was sensitive to the intracellular injection of Cl-, and was mimicked by the GABAA agonist muscimol. 3. The late IPSP, in contrast, had an average reversal potential of -95 mV, was associated with a mean 12-nS increase in membrane conductance, was reduced by the GABAB antagonist phaclofen, and was mimicked by the GABAB agonist baclofen. 4. Block of the early IPSP by bicuculline or picrotoxin led to the generation of paroxysmal epileptiform activity, which could be further enhanced by reduction of the late IPSP. 5. These data strongly support the hypothesis that GABA is a major inhibitory neurotransmitter in the human cerebral cortex and that GABAergic IPSPs play an important role in controlling the excitability and responsiveness of cortical neurons.

Baclofen↗
PubMed1988

Acetylcholine inhibits identified interneurons in the cat lateral geniculate nucleus.

The transmission of visual information from retina to cortex through the dorsal lateral geniculate nucleus (LGNd) is controlled by non-retinal inputs. Enhanced visually evoked responses in cat LGNd relay cells during periods of increased alertness have been attributed in large part to increased rate of acetylcholine (ACh) release by fibres ascending from the brainstem reticular formation. ACh can modulate geniculate visual responses in vivo, but comparatively little is known about the underlying ionic mechanisms of these cholinergic actions. Although direct excitation of LGNd relay neurons has been shown in vitro, the situation is complicated because cholinergic axons form numerous and complex synapses not only with relay cells, but also with inhibitory interneurons, and electrical activation of the brainstem cholinergic neurons reduces inhibitory postsynaptic potentials in the LGNd. We report here that morphologically characterized interneurons in the cat LGNd possess distinctive electrophysiological properties in comparison with those of relay cells and are inhibited by ACh through a muscarinic receptor-mediated increase in potassium conductance. Together the direct excitation of relay cells and inhibition of intrageniculate interneurons allow the ascending cholinergic system to exert a powerful facilitatory influence over the transfer of visual information to the cerebral cortex.

Acetylcholine↗
PubMed1988

Noradrenergic modulation of firing pattern in guinea pig and cat thalamic neurons, in vitro.

1. The electrophysiological actions of norepinephrine (NE) in the guinea pig and cat thalamus were investigated using intracellular recordings from neurons of in vitro thalamic slices. 2. Application of NE to neurons of the lateral and medial geniculate nuclei, nucleus reticularis, anteroventral nucleus, and the parataenial (PT) nucleus resulted in a slow depolarization associated with a 2- to 15-nS decrease in input conductance and an increase in the slow membrane time constant from an average of 27.7 to 37.7 ms. The slow depolarization was not abolished by blockade of synaptic transmission, indicating that it was a direct (postsynaptic) effect. 3. The reversal potential of the NE-induced slow depolarization varied as a Nernstian function of extracellular potassium concentration ([K]o), indicating that it is due to a decrease in potassium conductance. This conclusion was supported by the finding that the amplitude of the NE-evoked depolarization was affected by changes in [K]o between 0.5 and 5.0 mM as expected for a K-mediated response. 4. Neurons of the PT nucleus displayed unusually large afterhyperpolarizations (AHPs) in comparison to cells in other thalamic nuclei. NE application to PT neurons caused not only a marked slow depolarization and decreased conductance, but also selectively reduced the slow AHP. 5. The NE-induced slow depolarization effectively suppressed burst firing and promoted the occurrence of single spike activity. NE-induced reduction of the slow AHP in PT neurons was accompanied by a decrease in spike frequency accommodation and the emergence of a slow afterdepolarization. 6. We suggest that through these electrophysiological actions, NE can effectively inhibit the generation of thalamocortical rhythms and greatly facilitate the faithful transfer of information through the thalamus to the cerebral cortex.

Animals↗