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.

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.

Physiological Properties of Central Medial and Central Lateral Amygdala Neurons

1999 ◽  
Vol 82 (4) ◽  
pp. 1843-1854 ◽  
Author(s):  
Marzia Martina ◽  
Sébastien Royer ◽  
Denis Paré
Keyword(s):  
Conditioned Fear ◽  
Brain Slices ◽  
Cell Types ◽  
Membrane Depolarization ◽  
Membrane Properties ◽  
Repetitive Firing ◽  
Inward Rectification ◽  
Current Pulses ◽  
Outward Rectification ◽  
Physiological Properties

Mounting evidence implicates the central (CE) nucleus of the amygdala in the mediation of classically conditioned fear responses. However, little data are available regarding the intrinsic membrane properties of CE amygdala neurons. Here, we characterized the physiological properties of CE medial (CEM) and CE lateral (CEL) amygdala neurons using whole cell recordings in brain slices maintained in vitro. Several classes of CE neurons were distinguished on the basis of their physiological properties. Most CEM cells (95%), here termed “late-firing neurons,” displayed a marked voltage- and time-dependent outward rectification in the depolarizing direction. This phenomenon was associated with a conspicuous delay between the onset of depolarizing current pulses and the first action potential. During this delay, the membrane potential ( V m) depolarized slowly, the steepness of this depolarizing ramp increasing as the prepulse V m was hyperpolarized from −60 to −90 mV. Low extracellular concentrations of 4-aminopyridine (30 μM) reversibly abolished the outward rectification and the delay to firing. Late-firing CEM neurons displayed a continuum of repetitive firing properties with cells generating single spikes at one pole and high-frequency (≥90 Hz) spike bursts at the other. In contrast, only 56% of CEL cells displayed the late-firing behavior prevalent among CEM neurons. Moreover, these CEL neurons only generated single spikes in response to membrane depolarization. A second major class of CEL cells (38%) lacked the characteristic delay to firing observed in CEM cells, generated single spikes in response to membrane depolarization, and displayed various degrees of inward rectification in the hyperpolarizing direction. In both regions of the CE nucleus, two additional cell types were encountered infrequently (≤ 6% of our samples). One type of neurons, termed “low-threshold bursting cells” had a behavior reminiscent of thalamocortical neurons. The second type of cells, called “fast-spiking cells,” generated brief action potentials at high rates with little spike frequency adaptation in response to depolarizing current pulses. These findings indicate that the CE nucleus contains several types of neurons endowed with distinct physiological properties. Moreover, these various cell types are not distributed uniformly in the medial and lateral sector of the CE nucleus. This heterogeneity parallels anatomic data indicating that these subnuclei are part of different circuits.

Dendritic arbor of locus coeruleus neurons contributes to opioid inhibition

1996 ◽  
Vol 75 (5) ◽  
pp. 2029-2035 ◽  
Author(s):  
R. A. Travagli ◽  
M. Wessendorf ◽  
J. T. Williams
Keyword(s):  
Locus Coeruleus ◽  
Horizontal Plane ◽  
Reversal Potential ◽  
Outward Current ◽  
Membrane Properties ◽  
Equilibrium Potential ◽  
Intrinsic Membrane Properties ◽  
In Cells

1. The nucleus locus coeruleus (LC) is made up of noradrenergic cells all of which are hyperpolarized by opioids. Recent work has shown that the reversal potential of the opioid-induced current is more negative than the potassium equilibrium potential. The aim of the present study was to determine whether the extent of the dendritic field could contribute to the very negative opioid reversal potential. 2. Individual LC cells were labeled in the brain slice preparation. The number of dendrites found on cells in slices sectioned in the horizontal plane was greater than cells in coronal slices. However, the dimensions of the cell body slices from each plane were not significantly different. 3. The resting conductance of neurons from slices cut in the horizontal plane was significantly larger than in cells from coronal plane. 4. The amplitude of the outward current induced by [Met5]-enkephalin (ME) was larger in cells from horizontal slices and the reversal potential was more negative than that of cells in coronal slices. 5. The results show that the plane of section influences the membrane properties and opioid actions of LC neurons in vitro and suggest that these differences correlate with the numbers of dendrites. The results suggest that in vivo, in addition to intrinsic membrane properties and synaptic inputs, the structural makeup of the nucleus is an important factor in determining the activity.

scholarly journals Central blockade of oxytocin receptors during mid-late gestation reduces amplitude of slow afterhyperpolarization in supraoptic oxytocin neurons

2008 ◽  
Vol 295 (5) ◽  
pp. E1167-E1171 ◽  
Author(s):  
R. Teruyama ◽  
D. L. Lipschitz ◽  
L. Wang ◽  
G. R. Ramoz ◽  
W. R. Crowley ◽  
...  
Keyword(s):  
Third Ventricle ◽  
Late Gestation ◽  
Membrane Properties ◽  
Current Clamp ◽  
Pregnant Rats ◽  
Oxytocin Receptors ◽  
Artificial Cerebrospinal Fluid ◽  
Cell Current ◽  
Central Actions ◽  
Intrinsic Membrane Properties

The neurohypophysial hormone oxytocin (OT), synthesized in magnocellular paraventricular (PVN) and supraoptic (SON) nuclei, is well known for its effects in lactation. Our previous studies showed that central OT receptor (OTR) binding is increased during gestation and that blockade of central OTRs, specifically during mid-late gestation, causes a delay in OT release during suckling and reduces weight gain in pups, suggesting decreased milk delivery. In the present study, we tested whether central OTR blockade during late gestation disrupts the gestation-related plasticity in intrinsic membrane properties. Whole cell current-clamp recordings were performed in OT neurons from pregnant rats (19–22 days in gestation) that were infused with an OTR antagonist (OTA) or artificial cerebrospinal fluid (aCSF) and from virgin rats infused with aCSF into the third ventricle via an osmotic minipump beginning on days 12–14 of gestation. The amplitudes of both Ca2+-dependent afterhyperpolarizations (AHPs), an apamin-sensitive medium AHP (mAHP) and an apamin-insensitive slow AHP (sAHP), were significantly increased during late gestation in control pregnant animals. However, the amplitude of the sAHP from pregnant rats treated with the OTA was significantly smaller than that of pregnant control rats and similar to that of virgins. These results indicate that the diminished efficiency in lactation due to OTR blockade may be partly a result of an altered sAHP that would shape OT bursting. These findings suggest that central actions of OT during late gestation are necessary for programming the plasticity of at least some of the intrinsic membrane properties in OT neurons during lactation.

scholarly journals Regulation of Action Potential Size and Excitability in Substantia Nigra Compacta Neurons: Sensitivity to 4-Aminopyridine

1999 ◽  
Vol 82 (6) ◽  
pp. 2903-2913 ◽  
Author(s):  
S. Nedergaard
Keyword(s):  
Substantia Nigra ◽  
Time Window ◽  
Slow Component ◽  
Brain Slices ◽  
Membrane Properties ◽  
Initial Time ◽  
Direct Excitation ◽  
Spontaneous Action ◽  
Intrinsic Membrane Properties

Slow, pacemaker-like firing is due to intrinsic membrane properties in substantia nigra compacta (SNc) neurons in vitro. How these properties interact with afferent synaptic inputs is not fully understood. In this study, intracellular recordings from SNc neurons in brain slices showed that spontaneous action potentials (APs) were attenuated when generated from lower than normal threshold. Such APs were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and could be related to non– N-methyl-d-aspartate (NMDA) receptor–mediated spontaneous excitatory postsynaptic potentials (EPSPs). The AP attenuation was reproduced by stimulus-evoked EPSPs and by current injections to the soma. APs evoked from holding potentials between −40 and −60 mV were reduced in width by Cd2+ (0.2 mM). Tetraethylammonium chloride (TEA, 10 mM) or 4-aminopyridine (4-AP, 5 mM) increased the AP width. However, at more negative holding potentials, Cd2+ and TEA were inefficacious, whereas 4-AP enlarged the AP, partly via induction of a Cd2+-sensitive component. A monophasic afterhyperpolarization (AHP), following attenuated APs, was little affected by either Cd2+ or TEA, but inhibited by 4-AP, which induced an additional, slow component, sensitive to Cd2+ or apamin (100 nM). The AP delay showed a discontinuous relation to the amplitude or slope of the injected current (delay shift), which was sensitive to low doses of 4-AP (0.05 mM). The initial time window before the delay shift was longer than the rise time of EPSPs. It is suggested that a 4-AP–sensitive current prevents or postpones discharge during slow depolarization's, but allows direct excitation by fast EPSPs. Fast excitation leads to AP attenuation, primarily due to strong activation of 4-AP–sensitive current. This seems to cause inhibition of the Ca2+ current during the AP and reduction of Ca2+-dependent K+ currents. Together, these properties are likely to influence the excitability and the local, somatodendritic effects of the AP, in a manner that discriminates between firing induced by the intrinsic pacemaker mechanism and fast synaptic potentials.

scholarly journals Membrane and synaptic properties of pyramidal neurons in the anterior olfactory nucleus

2011 ◽  
Vol 105 (4) ◽  
pp. 1444-1453 ◽  
Author(s):  
Matthew J. McGinley ◽  
Gary L. Westbrook
Keyword(s):  
Pyramidal Neurons ◽  
Piriform Cortex ◽  
Brain Slices ◽  
Membrane Properties ◽  
Inward Rectification ◽  
Excitatory Synapses ◽  
Membrane Excitability ◽  
Anterior Olfactory Nucleus ◽  
Firing Rates ◽  
Synaptic Excitation

The anterior olfactory nucleus (AON) is positioned to coordinate activity between the piriform cortex and olfactory bulbs, yet the physiology of AON principal neurons has been little explored. Here, we examined the membrane properties and excitatory synapses of AON principal neurons in brain slices of PND22–28 mice and compared their properties to principal cells in other olfactory cortical areas. AON principal neurons had firing rates, spike rate adaptation, spike widths, and I-V relationships that were generally similar to pyramidal neurons in piriform cortex, and typical of cerebral cortex, consistent with a role for AON in cortical processing. Principal neurons in AON had more hyperpolarized action potential thresholds, smaller afterhyperpolarizations, and tended to fire doublets of action potentials on depolarization compared with ventral anterior piriform cortex and the adjacent epileptogenic region preendopiriform nucleus (pEN). Thus, AON pyramidal neurons have enhanced membrane excitability compared with surrounding subregions. Interestingly, principal neurons in pEN were the least excitable, as measured by a larger input conductance, lower firing rates, and more inward rectification. Afferent and recurrent excitatory synapses onto AON pyramidal neurons had small amplitudes, paired pulse facilitation at afferent synapses, and GABAB modulation at recurrent synapses, a pattern similar to piriform cortex. The enhanced membrane excitability and recurrent synaptic excitation within the AON, together with its widespread outputs, suggest that the AON can boost and distribute activity in feedforward and feedback circuits throughout the olfactory system.

scholarly journals GABAergic synaptic inputs of locus coeruleus neurons in wild-type and Mecp2-null mice

2013 ◽  
Vol 304 (9) ◽  
pp. C844-C857 ◽  
Author(s):  
Xin Jin ◽  
Ningren Cui ◽  
Weiwei Zhong ◽  
Xiao-Tao Jin ◽  
Chun Jiang
Keyword(s):  
Locus Coeruleus ◽  
Input Resistance ◽  
Gaba Release ◽  
Autism Spectrum ◽  
Membrane Properties ◽  
Postsynaptic Inhibition ◽  
Gene Encoding ◽  
Synaptic Inputs ◽  
Cell Current ◽  
The Central Nervous System

Rett syndrome is an autism spectrum disorder resulting from defects in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). Deficiency of the Mecp2 gene causes abnormalities in several systems in the brain, especially the norepinephrinergic and GABAergic systems. The norepinephrinergic neurons in the locus coeruleus (LC) modulate a variety of neurons and play an important role in multiple functions in the central nervous system. In Mecp2−/Y mice, defects in the intrinsic membrane properties of LC neurons have been identified, while how their synaptic inputs are affected remains unclear. Therefore, we performed these brain slice studies to demonstrate how LC neurons are regulated by GABAergic inputs and how such synaptic inputs are affected by Mecp2 knockout. In whole cell current clamp, the firing activity of LC neurons was strongly inhibited by the GABAA receptor agonist muscimol, accompanied by hyperpolarization and a decrease in input resistance. Such a postsynaptic inhibition was significantly reduced (by ∼30%) in Mecp2−/Y mice. Post- and presynaptic GABABergic inputs were found in LC neurons, which were likely mediated by the G protein-coupled, Ba2+-sensitive K+ channels. The postsynaptic GABABergic inhibition was deficient by ∼50% in Mecp2 knockout mice. Although the presynaptic GABABergic modulation appeared normal, both frequency and amplitude of the GABAAergic mIPSCs were drastically decreased (by 30–40%) in Mecp2-null mice. These results suggest that the Mecp2 disruption causes defects in both post- and presynaptic GABAergic systems in LC neurons, impairing GABAAergic and GABABergic postsynaptic inhibition and decreasing the GABA release from presynaptic terminals.

Modulation of Spontaneous Firing in Rat Subthalamic Neurons by 5-HT Receptor Subtypes

2005 ◽  
Vol 93 (3) ◽  
pp. 1145-1157 ◽  
Author(s):  
Zixiu Xiang ◽  
Lie Wang ◽  
Stephen T. Kitai
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Driving Forces ◽  
Brain Slices ◽  
Potassium Conductance ◽  
Firing Frequency ◽  
Membrane Properties ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Membrane Excitability

The subthalamic nucleus (STN) is considered to be one of the driving forces in the basal ganglia circuit. The STN is innervated by serotonergic afferents from the raphe nucleus and expresses a variety of 5-HT receptor subtypes. We investigated the effects of 5-HT and 5-HT receptor subtype agonists and antagonists on the firing properties of STN neurons in rat brain slices. We used cell-attached, perforated-patch, and whole cell recording techniques to detect changes in firing frequency and pattern and electrical membrane properties. Due to the depolarization of membrane potential caused by reduced potassium conductance, 5-HT (10 μM) increased the firing frequency of STN neurons without changing their firing pattern. Cadmium failed to occlude the effect of 5-HT on firing frequency. 5-HT had no effect on afterhyperpolarization current. These results indicated that the 5-HT action was not mediated by high-voltage–activated calcium channel currents and calcium-dependent potassium currents. 5-HT had no effect on hyperpolarization-activated cation current ( IH) amplitude and voltage-dependence of IH activation, suggesting that IH was not involved in 5-HT–induced excitation. The increased firing by 5-HT was mimicked by 5-HT2/4 receptor agonist α-methyl-5-HT and was partially mimicked by 5-HT2 receptor agonist DOI or 5-HT4 receptor agonist cisapride. The 5-HT action was partially reversed by 5-HT4 receptor antagonist SB 23597-190, 5-HT2 receptor antagonist ketanserin, and 5-HT2C receptor antagonist RS 102221. Our data indicate that 5-HT has significant ability to modulate membrane excitability in STN neurons; modulation is accomplished by decreasing potassium conductance by activating 5-HT4 and 5-HT2C receptors.

Response Sensitivity of Barrel Neuron Subpopulations to Simulated Thalamic Input

2010 ◽  
Vol 103 (6) ◽  
pp. 3001-3016 ◽  
Author(s):  
Michael J. Pesavento ◽  
Cynthia D. Rittenhouse ◽  
David J. Pinto
Keyword(s):  
Barrel Cortex ◽  
Brain Slices ◽  
Input Resistance ◽  
Inhibitory Neurons ◽  
Membrane Properties ◽  
Cortical Function ◽  
Thalamic Input ◽  
Intrinsic Membrane Properties

Our goal is to examine the relationship between neuron- and network-level processing in the context of a well-studied cortical function, the processing of thalamic input by whisker-barrel circuits in rodent neocortex. Here we focus on neuron-level processing and investigate the responses of excitatory and inhibitory barrel neurons to simulated thalamic inputs applied using the dynamic clamp method in brain slices. Simulated inputs are modeled after real thalamic inputs recorded in vivo in response to brief whisker deflections. Our results suggest that inhibitory neurons require more input to reach firing threshold, but then fire earlier, with less variability, and respond to a broader range of inputs than do excitatory neurons. Differences in the responses of barrel neuron subtypes depend on their intrinsic membrane properties. Neurons with a low input resistance require more input to reach threshold but then fire earlier than neurons with a higher input resistance, regardless of the neuron's classification. Our results also suggest that the response properties of excitatory versus inhibitory barrel neurons are consistent with the response sensitivities of the ensemble barrel network. The short response latency of inhibitory neurons may serve to suppress ensemble barrel responses to asynchronous thalamic input. Correspondingly, whereas neurons acting as part of the barrel circuit in vivo are highly selective for temporally correlated thalamic input, excitatory barrel neurons acting alone in vitro are less so. These data suggest that network-level processing of thalamic input in barrel cortex depends on neuron-level processing of the same input by excitatory and inhibitory barrel neurons.

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