Electrophysiological Properties of Cholinergic and Noncholinergic Neurons in the Ventral Pallidal Region of the Nucleus Basalis in Rat Brain Slices

2000 ◽  
Vol 83 (5) ◽  
pp. 2649-2660 ◽  
Author(s):  
C. Peter Bengtson ◽  
Peregrine B. Osborne
Keyword(s):  
Brain Slices ◽  
Physiological Role ◽  
Cholinergic Neurons ◽  
Firing Frequency ◽  
Nucleus Basalis ◽  
Morphological Properties ◽  
Inward Rectification ◽  
Resting Membrane Potential ◽  
Whole Cell ◽  
Electrophysiological Properties

The ventral pallidum is a major source of output for ventral corticobasal ganglia circuits that function in translating motivationally relevant stimuli into adaptive behavioral responses. In this study, whole cell patch-clamp recordings were made from ventral pallidal neurons in brain slices from 6- to 18-day-old rats. Intracellular filling with biocytin was used to correlate the electrophysiological and morphological properties of cholinergic and noncholinergic neurons identified by choline acetyltransferase immunohistochemistry. Most cholinergic neurons had a large whole cell conductance and exhibited marked fast (i.e., anomalous) inward rectification. These cells typically did not fire spontaneously, had a hyperpolarized resting membrane potential, and also exhibited a prominent spike afterhyperpolarization (AHP) and strong spike accommodation. Noncholinergic neurons had a smaller whole cell conductance, and the majority of these cells exhibited marked time-dependent inward rectification that was due to an h-current. This current activated slowly over several hundred milliseconds at potentials more negative than −80 mV. Noncholinergic neurons fired tonically in regular or intermittent patterns, and two-thirds of the cells fired spontaneously. Depolarizing current injection in current clamp did not cause spike accommodation but markedly increased the firing frequency and in some cells also altered the pattern of firing. Spontaneous tetrodotoxin-sensitive GABAA-mediated inhibitory postsynaptic currents (IPSCs) were frequently recorded in noncholinergic neurons. These results show that cholinergic pallidal neurons have similar properties to magnocellular cholinergic neurons in other parts of the forebrain, except that they exhibit strong spike accommodation. Noncholinergic ventral pallidal neurons have large h-currents that could have a physiological role in determining the rate or pattern of firing of these cells.

scholarly journals Knockouts reveal overlapping functions of M2 and M4 muscarinic receptors and evidence for a local glutamatergic circuit within the laterodorsal tegmental nucleus

2012 ◽  
Vol 108 (10) ◽  
pp. 2751-2766 ◽  
Author(s):  
Kristi A. Kohlmeier ◽  
Masaru Ishibashi ◽  
Jürgen Wess ◽  
Martha E. Bickford ◽  
Christopher S. Leonard
Keyword(s):  
Acetylcholine Receptors ◽  
Brain Slices ◽  
Cholinergic Neurons ◽  
Muscarinic Acetylcholine Receptors ◽  
Feedback Signal ◽  
Laterodorsal Tegmental Nucleus ◽  
Membrane Hyperpolarization ◽  
Whole Cell ◽  
Whole Cell Recording ◽  
Cell Recording

Cholinergic neurons in the laterodorsal tegmental (LDT) and peduncolopontine tegmental (PPT) nuclei regulate reward, arousal, and sensory gating via major projections to midbrain dopamine regions, the thalamus, and pontine targets. Muscarinic acetylcholine receptors (mAChRs) on LDT neurons produce a membrane hyperpolarization and inhibit spike-evoked Ca2+ transients. Pharmacological studies suggest M2 mAChRs are involved, but the role of these and other localized mAChRs (M1--M4) has not been definitively tested. To identify the underlying receptors and to circumvent the limited receptor selectivity of available mAChR ligands, we used light- and electron-immunomicroscopy and whole cell recording with Ca2+ imaging in brain slices from knockout mice constitutively lacking either M2, M4, or both mAChRs. Immunomicroscopy findings support a role for M2 mAChRs, since cholinergic and noncholinergic LDT and pedunculopontine tegmental neurons contain M2-specific immunoreactivity. However, whole cell recording revealed that the presence of either M2 or M4 mAChRs was sufficient, and that the presence of at least one of these receptors was required for these carbachol actions. Moreover, in the absence of M2 and M4 mAChRs, carbachol elicited both direct excitation and barrages of spontaneous excitatory postsynaptic potentials (sEPSPs) in cholinergic LDT neurons mediated by M1 and/or M3 mAChRs. Focal carbachol application to surgically reduced slices suggest that local glutamatergic neurons are a source of these sEPSPs. Finally, neither direct nor indirect excitation were knockout artifacts, since each was detected in wild-type slices, although sEPSP barrages were delayed, suggesting M2 and M4 receptors normally delay excitation of glutamatergic inputs. Collectively, our findings indicate that multiple mAChRs coordinate cholinergic outflow from the LDT in an unexpectedly complex manner. An intriguing possibility is that a local circuit transforms LDT muscarinic inputs from a negative feedback signal for transient inputs into positive feedback for persistent inputs to facilitate different firing patterns across behavioral states.

Postnatal Development of Electrophysiological Properties of Nucleus Accumbens Neurons

2000 ◽  
Vol 84 (5) ◽  
pp. 2204-2216 ◽  
Author(s):  
Marc L. Belleau ◽  
Richard A. Warren
Keyword(s):  
Nucleus Accumbens ◽  
Postnatal Development ◽  
Action Potentials ◽  
Membrane Resistance ◽  
Inward Rectification ◽  
Resting Membrane Potential ◽  
Projection Neurons ◽  
Patch Clamp Technique ◽  
Whole Cell ◽  
Wide Range

We have studied the postnatal development of the physiological characteristics of nucleus accumbens (nAcb) neurons in slices from postnatal day 1 ( P1) to P49 rats using the whole cell patch-clamp technique. The majority of neurons (102/108) were physiologically identified as medium spiny (MS) projection neurons, and only these were subjected to detailed analysis. The remaining neurons displayed characteristics suggesting that they were not MS neurons. Around the time of birth and during the first postnatal weeks, the membrane and firing characteristics of MS neurons were quite different from those observed later. These characteristics changed rapidly during the first 3 postnatal weeks, at which point they began to resemble those found in adults. Both whole cell membrane resistance and membrane time constant decreased more than fourfold during the period studied. The resting membrane potential (RMP) also changed significantly from an average of −50 mV around birth to less than −80 mV by the end of the third postnatal week. During the first postnatal week, the current-voltage relationship of all encountered MS neurons was linear over a wide range of membrane potentials above and below RMP. Through the second postnatal week, the proportion of neurons displaying inward rectification in the hyperpolarized range increased steadily and after P15, all recorded MS neurons displayed significant inward rectification. At all ages, inward rectification was blocked by extracellular cesium and tetra-ethyl ammonium and was not changed by 4-aminopyridine; this shows that inward rectification was mediated by the same currents in young and mature MS neurons. MS neurons fired single and repetitive Na+/K+ action potentials as early as P1. Spike threshold and amplitude remained constant throughout development in contrast to spike duration, which decreased significantly over the same period. Depolarizing current pulses from rest showed that immature MS neurons fired action potentials more easily than their older counterparts. Taken together, the results from the present study suggest that young and adult nAcb MS neurons integrate excitatory synaptic inputs differently because of differences in their membrane and firing properties. These findings provide important insights into signal processing within nAcb during this critical period of development.

Electrophysiological properties and synaptic responses in the deep layers of the human epileptogenic neocortex in vitro

1989 ◽  
Vol 61 (3) ◽  
pp. 589-606 ◽  
Author(s):  
M. Avoli ◽  
A. Olivier
Keyword(s):  
Epileptiform Activity ◽  
Equilibrium Potential ◽  
Repetitive Firing ◽  
Inward Rectification ◽  
Resting Membrane Potential ◽  
Linear Segment ◽  
Electrophysiological Properties ◽  
Deep Layers ◽  
Synaptic Responses

1. Neocortical slices of the first and second temporal gyrus and frontal lobe, removed in human epileptic patients for the relief of intractable seizures, were maintained in vitro at 35 +/- 1 degrees C. Electrophysiological properties of neurons in the deep layers (1,800–2,600 micron below the pial surface) were studied with conventional intracellular recording and stimulation techniques. Synaptic responses were evoked by extracellular focal stimuli. Intracellular injections of some cells with the fluorescent dye Lucifer yellow revealed large spiny pyramidal neurons. 2. Values of input resistance, resting membrane potential (Vm), and action-potential amplitude were similar for neurons in different cortical regions. These parameters were also similar when neurons were grouped in accordance to the degree of electrographic epileptiform activity displayed by the cortical tissue in situ. 3. Inward rectification occurred when neurons were depolarized by 5–15 mV positive to the resting Vm. This rectification was abolished by extracellular application of tetrodotoxin (TTX, 1 microM), but was still observed in the presence of the Ca2+-channel blocker Cd2+ (2 mM). Pulses of hyperpolarizing current elicited a slowly developing inward rectification, called anomalous rectification, which was insensitive to TTX, but blocked by extracellular application of Cs+ (1-2 mM). 4. Intracellular injection of depolarizing square pulses of current (0.1-4 s) evoked repetitive firing. In most cells the firing rate decreased smoothly for tens of milliseconds (i.e., it adapted) before reaching a steady level. Plots of the relation between frequency of the repetitive firing and injected current (f-I curve) displayed two linear segments for the early intervals as well as for the adapted and/or the steady firing. The slope of the initial, steeper linear segment of the f-I curve computed during the early intervals and during the adapted firing was 163 +/- 51 and 56 +/- 27 (SD) Hz/nA, respectively. 5. A long-lasting (up to 8 s) afterhyperpolarization (AHP) followed the repetitive firing induced by square pulses of depolarizing current. Its amplitude was directly proportional to the amount of current injected, it was sensitive to changes in the Vm, and it had an equilibrium potential 10–40 mV negative to the resting Vm. This value plus the fact that the AHP could be recorded with KCl-filled microelectrodes suggested that it was caused by an increase in conductance to K+ ions. Bath application of the Ca2+ channel blockers Cd2+ (2 mM) or Mn2+ (2 mM) decreased and eventually blocked the AHP.(ABSTRACT TRUNCATED AT 400 WORDS)

Membrane properties of rat subicular neurons in vitro

1993 ◽  
Vol 70 (3) ◽  
pp. 1244-1248 ◽  
Author(s):  
D. Mattia ◽  
G. G. Hwa ◽  
M. Avoli
Keyword(s):  
Hippocampal Slices ◽  
Rhythmic Activity ◽  
Input Resistance ◽  
Membrane Properties ◽  
Inward Rectification ◽  
Resting Membrane Potential ◽  
Channel Blockers ◽  
Electrophysiological Properties ◽  
Low Threshold

1. Conventional intracellular recordings were performed in rat hippocampal slices to investigate the electrophysiological properties of subicular neurons. These cells had a resting membrane potential (RMP) of -66 +/- 7.2 mV (mean +/- SD; n = 50), input resistance of 23.6 +/- 8.2 M omega (n = 51), time constant of 7.1 +/- 1.9 ms (n = 51), action potential amplitude of 85.8 +/- 13.8 mV (n = 50), and duration of 2.9 +/- 1.2 ms (n = 48). Analysis of the current-voltage relationship revealed membrane inward rectification in both depolarizing and hyperpolarizing direction. The latter type was readily abolished by Cs+ (3 mM; n = 6 cells). 2. Injection of depolarizing current pulses of threshold intensity induced in all subicular neurons (n = 51) recorded at RMP a burst of two to three fast action potentials (frequency = 212.7 +/- 90 Hz, n = 13 cells). This burst rode on a slow depolarizing envelope and was followed by an afterhyperpolarization and later by regular spiking mode once the pulse was prolonged. Similar bursts were also generated upon termination of a hyperpolarizing current pulse. 3. The slow depolarization underlying the burst resembled a low-threshold response, which in thalamic cells is caused by a Ca2+ conductance and is contributed by the Cs(+)-sensitive inward rectifier. However, bursts in subicular cells persisted in medium containing the Ca(2+)-channel blockers Co2+ (2 mM) and Cd2+ (1 mM) (n = 5 cells) but disappeared during application of TTX (1 microM; n = 3 cells). Hence they were mediated by Na+. Blockade of the hyperpolarizing inward rectification by Cs+ did not prevent the rebound response (n = 3 cells). 4. Our findings demonstrate that intrinsic bursts, presumably related to a "low-threshold" Na+ conductance are present in rat subicular neurons. Similar intrinsic characteristics have been suggested to underlie the rhythmic activity described in other neuronal networks, although in most cases the low-threshold electrogenesis was caused by Ca2+. We propose that the bursting mechanism might play a role in modulating incoming signals from the classical hippocampal circuit within the limbic system.

A maturational shift in pulmonary K+ channels, from Ca2+ sensitive to voltage dependent

1998 ◽  
Vol 275 (6) ◽  
pp. L1019-L1025 ◽  
Author(s):  
Helen L. Reeve ◽  
E. Kenneth Weir ◽  
Stephen L. Archer ◽  
David N. Cornfield
Keyword(s):  
Pulmonary Circulation ◽  
Acute Hypoxia ◽  
Outward Current ◽  
Resting Membrane Potential ◽  
Transient Outward Current ◽  
Abrupt Decrease ◽  
Whole Cell ◽  
Electrophysiological Properties ◽  
Voltage Dependent ◽  
Intracellular Ca

The mechanism responsible for the abrupt decrease in resistance of the pulmonary circulation at birth may include changes in the activity of O2-sensitive K+ channels. We characterized the electrophysiological properties of fetal and adult ovine pulmonary arterial (PA) smooth muscle cells (SMCs) using conventional and amphotericin B-perforated patch-clamp techniques. Whole cell K+ currents of fetal PASMCs in hypoxia were small and characteristic of spontaneously transient outward currents. The average resting membrane potential (RMP) was −36 ± 3 mV and could be depolarized by charybdotoxin (100 nM) or tetraethylammonium chloride (5 mM; both blockers of Ca2+-dependent K+ channels) but not by 4-aminopyridine (4-AP; 1 mM; blocker of voltage-gated K+ channels) or glibenclamide (10 μM; blocker of ATP-dependent K+channels). In hypoxia, chelation of intracellular Ca2+ by 5 mM 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid further reduced the amplitude of the whole cell K+ current and prevented spontaneously transient outward current activity. Under these conditions, the remaining current was partially inhibited by 1 mM 4-AP. K+ currents of fetal PASMCs maintained in normoxia were not significantly reduced by acute hypoxia. In normoxic adult PASMCs, whole cell K+ currents were large and RMP was −49 ± 3 mV. These 4-AP-sensitive K+ currents were partially inhibited by exposure to acute hypoxia. We conclude that the K+ channel regulating RMP in the ovine pulmonary circulation changes after birth from a Ca2+-dependent K+ channel to a voltage-dependent K+ channel. The maturational-dependent differences in the mechanism of the response to acute hypoxia may be due to this difference in K+ channels.

scholarly journals Early postnatal development of the cellular and circuit properties of striatal D1 and D2 spiny projection neurons

2018 ◽  
Author(s):  
Rohan N. Krajeski ◽  
Anežka Macey-Dare ◽  
Fran van Heusden ◽  
Farid Ebrahimjee ◽  
Tommas J. Ellender
Keyword(s):  
Neurodevelopmental Disorders ◽  
Neural Circuit ◽  
Quantitative Description ◽  
Brain Slices ◽  
Morphological Properties ◽  
Projection Neurons ◽  
Normal Brain ◽  
Early Postnatal Development ◽  
Electrophysiological Properties ◽  
Cortical Inputs

AbstractA dysfunctional striatum is thought to contribute to neurodevelopmental disorders such as ADHD, Tourette’s syndrome and OCD. Insight into these disorders is reliant on an understanding of the normal development of the striatal cellular and circuit properties. Here we combined whole-cell patch-clamp electrophysiology and anatomical reconstructions of D1 and D2 striatal projection neurons (SPNs) in brain slices to characterize the development of the electrophysiological and morphological properties as well as their long-range and local inputs during the first three postnatal weeks. Overall, we find that many properties develop in parallel but we make several key observations. Firstly, that the electrophysiological properties of young D1 SPNs are more mature and that distinctions between D1 and D2 SPNs become apparent in the second postnatal week. Secondly, that dendrites and spines as well as excitatory inputs from cortex develop in parallel with cortical inputs exhibiting a prolonged period of maturation involving changes in postsynaptic glutamate receptors. Lastly, that initial local connections between striatal SPNs consist of gap junctions, which are gradually replaced by inhibitory synaptic connections. Interestingly, relative biases in inhibitory synaptic connectivity seen between SPNs in adulthood, such as a high connectivity between D2 SPNs, are already evident in the second postnatal week. Combined, these results provide an experimental framework for future investigations of striatal neurodevelopmental disorders and show that many of the cellular and circuit properties are established in the first and second postnatal weeks suggesting intrinsic programs guide their development.Significance StatementNormal brain development involves the formation of neurons, which develop correct electrical and morphological properties and are precisely connected with each other in a neural circuit. In neurodevelopmental disorders these processes go awry leading to behavioral and cognitive problems later in life. Here we provide for the first time a detailed quantitative description of the cellular and circuit properties of the two main neuron types of the striatum during the first postnatal weeks. This can form an experimental framework for future studies into neurodevelopmental disorders. We find that most of the properties for both types of striatal neuron develop in parallel and are already established by the second postnatal week suggesting a key role for intrinsic programs in guiding their development.

Development of Inward Rectification and Control of Membrane Excitability in Mesencephalic V Neurons

2003 ◽  
Vol 89 (3) ◽  
pp. 1288-1298 ◽  
Author(s):  
Susumu Tanaka ◽  
Nanping Wu ◽  
Chie-Fang Hsaio ◽  
Jack Turman ◽  
Scott H. Chandler
Keyword(s):  
Cell Voltage ◽  
Resting Potential ◽  
Inward Rectification ◽  
Resting Membrane Potential ◽  
Membrane Excitability ◽  
Membrane Hyperpolarization ◽  
Whole Cell ◽  
Membrane Resonance ◽  
And Control ◽  
Zd 7288

The present study was performed to assess the postnatal development and functional roles of inward rectifying currents in rat mesencephalic trigeminal (Mes V) neurons, which are involved in the genesis and control of oral-motor activities. Whole cell voltage-clamp recordings obtained from Mes V neurons in brain stem slices identified fast ( I KIR) and slow ( I h) inward rectifying currents, which were specifically blocked by BaCl2 (300–500 μM) or 4-( N-ethyl- N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride (ZD 7288, 10 μM), respectively. The whole cell current density for these channels increased between postnatal days 2 to 12 (P2-P12), and the time courses for I h activation and deactivation were each well described by two time constants. Application of ZD 7288 produced membrane hyperpolarization in the majority of cells and prolonged afterhyperpolarization repolarization. Additionally, in the presence of ZD 7288, spike frequency was decreased and adaptation was more pronounced. Interestingly, these neurons exhibited a voltage-dependent membrane resonance (<10 Hz) that was prominent around resting potential and more negative to rest and was blocked by ZD 7288. These results suggest that I hcontributes to stabilizing resting membrane potential and controlling cell excitability. The presence of I himparts the neuron with the unique property of low-frequency membrane resonance; the ability to discriminate between synaptic inputs based on frequency content.

α5GABAA Receptors Regulate the Intrinsic Excitability of Mouse Hippocampal Pyramidal Neurons

2007 ◽  
Vol 98 (4) ◽  
pp. 2244-2254 ◽  
Author(s):  
Robert P. Bonin ◽  
Loren J. Martin ◽  
John F. MacDonald ◽  
Beverley A. Orser
Keyword(s):  
Action Potential ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Physiological Role ◽  
Network Activity ◽  
Equilibrium Potential ◽  
Resting Membrane Potential ◽  
Action Potential Firing ◽  
Membrane Hyperpolarization ◽  
Hippocampal Pyramidal Neurons

GABAA receptors generate both phasic and tonic forms of inhibition. In hippocampal pyramidal neurons, GABAA receptors that contain the α5 subunit generate a tonic inhibitory conductance. The physiological role of this tonic inhibition is uncertain, although α5GABAA receptors are known to influence hippocampal-dependent learning and memory processes. Here we provide evidence that α5GABAA receptors regulate the strength of the depolarizing stimulus that is required to generate an action potential in pyramidal neurons. Neurons from α5 knock-out (α5−/−) and wild-type (WT) mice were studied in brain slices and cell cultures using whole cell and perforated-patch-clamp techniques. Membrane resistance was 1.6-fold greater in α5−/− than in WT neurons, but the resting membrane potential and chloride equilibrium potential were similar. Membrane hyperpolarization evoked by an application of exogenous GABA was greater in WT neurons. Inhibiting the function of α5GABAA receptor with nonselective (picrotoxin) or α5 subunit-selective (L-655,708) compounds depolarized WT neurons by ∼3 mV, whereas no change was detected in α5−/− neurons. The depolarizing current required to generate an action potential was twofold greater in WT than in α5−/− neurons, whereas the slope of the input-output relationship for action potential firing was similar. We conclude that shunting inhibition mediated by α5GABAA receptors regulates the firing of action potentials and may synchronize network activity that underlies hippocampal-dependent behavior.

Direct Actions of Cannabinoids on Synaptic Transmission in the Nucleus Accumbens: A Comparison With Opioids

2001 ◽  
Vol 85 (1) ◽  
pp. 72-83 ◽  
Author(s):  
Alexander F. Hoffman ◽  
Carl R. Lupica
Keyword(s):  
Nucleus Accumbens ◽  
Synaptic Transmission ◽  
Drugs Of Abuse ◽  
Glutamate Release ◽  
Brain Slices ◽  
Resting Membrane Potential ◽  
Projection Neurons ◽  
Whole Cell ◽  
Postsynaptic Currents ◽  
Abused Drugs

The nucleus accumbens (NAc) represents a critical site for the rewarding and addictive properties of several classes of abused drugs. The medium spiny GABAergic projection neurons (MSNs) in the NAc receive innervation from intrinsic GABAergic interneurons and glutamatergic innervation from extrinsic sources. Both GABA and glutamate release onto MSNs are inhibited by drugs of abuse, suggesting that this action may contribute to their rewarding properties. To investigate the actions of cannabinoids in the NAc, we performed whole cell recordings from MSNs located in the shell region in rat brain slices. The cannabinoid agonist WIN 55,212-2 (1 μM) had no effect on the resting membrane potential, input resistance, or whole cell conductance, suggesting no direct postsynaptic effects. Evoked glutamatergic excitatory postsynaptic currents (EPSCs) were inhibited to a much greater extent by [Tyr-d-Ala2, N-CH3-Phe4, Gly-ol-enkephalin] (DAMGO, ∼35%) than by WIN 55,212-2 (<20%), and an analysis of miniature EPSCs suggested that the effects of DAMGO were presynaptic, whereas those of WIN 55,212-2 were postsynaptic. However, electrically evoked GABAergic inhibitory postsynaptic currents (evIPSCs), were reduced by WIN 55,212-2 in every neuron tested (EC50 = 123 nM; 60% maximal inhibition), and the inhibition of IPSCs by WIN 55,212-2 was completely antagonized by the CB1 receptor antagonist SR141716A (1 μM). In contrast evIPSCs were inhibited in ∼50% of MSNs by the μ/δ opioid agonistd-Ala2-methionine2-enkephalinamide and were completely unaffected by a selective μ-opioid receptor agonist (DAMGO). WIN 55,212-2 also increased paired-pulse facilitation of the evIPSCs and did not alter the amplitudes of tetrodotoxin-resistant miniature IPSCs, suggesting a presynaptic action. Taken together, these data suggest that cannabinoids and opioids differentially modulate inhibitory and excitatory synaptic transmission in the NAc and that the abuse liability of marijuana may be related to the direct actions of cannabinoids in this structure.

scholarly journals Intrinsic membrane properties of locus coeruleus neurons in Mecp2-null mice

2010 ◽  
Vol 298 (3) ◽  
pp. C635-C646 ◽  
Author(s):  
Xiaoli Zhang ◽  
Ningren Cui ◽  
Zhongying Wu ◽  
Junda Su ◽  
Jyothirmayee S. Tadepalli ◽  
...  
Keyword(s):  
Locus Coeruleus ◽  
Rett Syndrome ◽  
Brain Slices ◽  
Firing Frequency ◽  
Membrane Properties ◽  
Inward Rectification ◽  
Frequency Variation ◽  
Norepinephrine System ◽  
Cell Current ◽  
Intrinsic Membrane Properties

Rett syndrome caused by mutations in methyl-CpG-binding protein 2 ( Mecp2) gene shows abnormalities in autonomic functions in which brain stem norepinephrinergic systems play an important role. Here we present systematic comparisons of intrinsic membrane properties of locus coeruleus (LC) neurons between Mecp2−/Y and wild-type (WT) mice. Whole cell current clamp was performed in brain slices of 3- to 4-wk-old mice. Mecp2−/Y neurons showed stronger inward rectification and had shorter time constant than WT cells. The former was likely due to overexpression of inward rectifier K+ (Kir)4.1 channel, and the latter was attributable to the smaller cell surface area. The action potential duration was prolonged in Mecp2−/Y cells with an extended rise time. This was associated with a significant reduction in the voltage-activated Na+ current density. After action potentials, >60% Mecp2−/Y neurons displayed fast and medium afterhyperpolarizations (fAHP and mAHP), while nearly 90% WT neurons showed only mAHP. The mAHP amplitude was smaller in Mecp2−/Y neurons. The firing frequency was higher in neurons with mAHP, and the frequency variation was greater in cells with both fAHP and mAHP in Mecp2−/Y mice. Small but significant differences in spike frequency adaptation and delayed excitation were found in Mecp2−/Y neurons. These results indicate that there are several electrophysiological abnormalities in LC neurons of Mecp2−/Y mice, which may contribute to the dysfunction of the norepinephrine system in Rett syndrome.

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