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.

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.

Vasopressin Increases GABAergic Inhibition of Rat Hypothalamic Paraventricular Nucleus Neurons In Vitro

2000 ◽  
Vol 83 (2) ◽  
pp. 705-711 ◽  
Author(s):  
M.L.H.J. Hermes ◽  
J. M. Ruijter ◽  
A. Klop ◽  
R. M. Buijs ◽  
L. P. Renaud
Keyword(s):  
Paraventricular Nucleus ◽  
Receptor Agonist ◽  
Hypothalamic Paraventricular Nucleus ◽  
Membrane Properties ◽  
Magnocellular Neurons ◽  
Membrane Hyperpolarization ◽  
Perforated Patch ◽  
Intrinsic Membrane Properties ◽  
Brain Slice Preparation

This investigation used an in vitro hypothalamic brain slice preparation and whole cell and perforated-patch recording to examine the response of magnocellular neurons in hypothalamic paraventricular nucleus (PVN) to bath applications of vasopressin (VP; 100–500 nM). In 22/38 cells, responses were characterized by an increase in the frequency of bicuculline-sensitive inhibitory postsynaptic potentials or currents with no detectable influence on excitatory postsynaptic events. Perforated-patch recordings confirmed that VP did not have an effect on intrinsic membrane properties of magnocellular PVN neurons ( n = 17). Analysis of intrinsic membrane properties obtained with perforated-patch recording ( n = 23) demonstrated that all of nine VP-sensitive neurons showed a rebound depolarization after transient membrane hyperpolarization from rest. By contrast, 12/14 nonresponding neurons displayed a delayed return to resting membrane potentials. Recordings of reversed inhibitory postsynaptic currents with chloride-loaded electrodes showed that responses to VP persisted in media containing glutamate receptor antagonists but were abolished in the presence of tetrodotoxin. In addition, responses were mimicked by vasotocin [Phe2, Orn8], a selective V1a receptor agonist, and blocked by [β-Mercapto-β,β-cyclopentamethylenepropionyl1,O-Me-Tyr2, Arg8]-VP (Manning compound), a V1a/OT receptor antagonist. Neither [deamino-Cys1,Val4,d-Arg8]-VP, a selective V2 receptor agonist, nor oxytocin were effective. Collectively, the results imply that VP acts at V1a receptors to excite GABAergic neurons that are presynaptic to a population of magnocellular PVN neurons the identity of which features a unique rebound depolarization. Endogenous sources of VP may be VP-synthesizing neurons in suprachiasmatic nucleus, known to project toward the perinuclear regions of PVN, and/or the magnocellular neurons within PVN.

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.

Membrane Properties Underlying Patterns of GABA-Dependent Action Potentials in Developing Mouse Hypothalamic Neurons

2001 ◽  
Vol 86 (3) ◽  
pp. 1252-1265 ◽  
Author(s):  
Yu-Feng Wang ◽  
Xiao-Bing Gao ◽  
Anthony N. van den Pol
Keyword(s):  
Membrane Potential ◽  
Action Potentials ◽  
Brain Slices ◽  
Reversal Potential ◽  
Membrane Properties ◽  
Resting Membrane Potential ◽  
Hypothalamic Neurons ◽  
Spike Threshold ◽  
Spike Patterns

Spikes may play an important role in modulating a number of aspects of brain development. In early hypothalamic development, GABA can either evoke action potentials, or it can shunt other excitatory activity. In both slices and cultures of the mouse hypothalamus, we observed a heterogeneity of spike patterns and frequency in response to GABA. To examine the mechanisms underlying patterns and frequency of GABA-evoked spikes, we used conventional whole cell and gramicidin perforation recordings of neurons ( n = 282) in slices and cultures of developing mouse hypothalamus. Recorded with gramicidin pipettes, GABA application evoked action potentials in hypothalamic neurons in brain slices of postnatal day 2–9( P2- 9) mice. With conventional patch pipettes (containing 29 mM Cl−), action potentials were also elicited by GABA from neurons of 2–13 days in vitro (2–13 DIV) embryonic hypothalamic cultures. Depolarizing responses to GABA could be generally classified into three types: depolarization with no spike, a single spike, or complex patterns of multiple spikes. In parallel experiments in slices, electrical stimulation of GABAergic mediobasal hypothalamic neurons in the presence of glutamate receptor antagonists [10 μM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 100 μM 2-amino-5-phosphonopentanoic acid (AP5)] resulted in the occurrence of spikes that were blocked by bicuculline (20 μM). Blocking ionotropic glutamate receptors with AP5 and CNQX did not block GABA-mediated multiple spikes. Similarly, when synaptic transmission was blocked with Cd2+ (200 μM) and Ni2+(300 μM), GABA still induced multiple spikes, suggesting that the multiple spikes can be an intrinsic membrane property of GABA excitation and were not based on local interneurons. When the pipette [Cl−] was 29 or 45 mM, GABA evoked multiple spikes. In contrast, spikes were not detected with 2 or 10 mM intracellular [Cl−]. With gramicidin pipettes, we found that the mean reversal potential of GABA-evoked current ( E GABA) was positive to the resting membrane potential, suggesting a high intracellular [Cl−] in developing mouse neurons. Varying the holding potential from −80 to 0 mV revealed an inverted U-shaped effect on spike probability. Blocking voltage-dependent Na+ channels with tetrodotoxin eliminated GABA-evoked spikes, but not the GABA-evoked depolarization. Removing Ca2+ from the extracellular solution did not block spikes, indicating GABA-evoked Na+-based spikes. Although E GABA was more positive within 2–5 days in culture, the probability of GABA-evoked spikes was greater in 6- to 9-day cells. Mechanistically, this appears to be due to a greater Na+ current found in the older cells during a period when the E GABA is still positive to the resting membrane potential. GABA evoked similar spike patterns in HEPES and bicarbonate buffers, suggesting that Cl−, not bicarbonate, was primarily responsible for generatingmultiple spikes. GABA evoked either single or multiple spikes; neurons with multiple spikes had a greater Na+ current, a lower conductance, a more negative spike threshold, and a greater difference between the peak of depolarization and the spike threshold. Taken together, the present results indicate that the patterns of multiple action potentials evoked by GABA are an inherent property of the developing hypothalamic neuron.

scholarly journals Dendritic Projections and Dye-Coupling in Dopaminergic Neurons of the Substantia Nigra Examined in Horizontal Brain Slices From Young Rats

2003 ◽  
Vol 90 (4) ◽  
pp. 2531-2535 ◽  
Author(s):  
John Y. Lin ◽  
Michiel van Wyk ◽  
Tharushini K. Bowala ◽  
Min-Yau Teo ◽  
Janusz Lipski
Keyword(s):  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Lucifer Yellow ◽  
Brain Slices ◽  
Positive Control ◽  
Substantia Nigra Pars Compacta ◽  
Dye Coupling ◽  
Whole Cell ◽  
Connexin 36

We examined the rostro-caudal dendritic spread of striatally projecting dopaminergic neurons of the Substantia Nigra pars compacta (SNc) and investigated the presence of dye-coupling after labeling these cells with a mixture of lucifer yellow (LY) and neurobiotin (NB) or with LY alone. Whole cell recordings were made from horizontal brain slices (400 μm) obtained from P5-P20 rats. SNc neurons retrogradely labeled with Fluoro-Gold and located in the region containing tyrosine hydroxylase-immunoreactive cells displayed Ih current and other properties characteristic of SNc neurons. To prevent extracellular leakage, dyes were introduced into patch pipettes after the establishment of whole cell configuration, and cells were filled under visual control. In contrast to previous studies conducted in coronal sections that identified dendritic projections of SNc neurons mainly in the medio-lateral and ventral directions, almost all neurons labeled in our study (53/54) additionally displayed a large rostro-caudal dendritic span (649 ± 219 μm). Dye-coupling between SNc neurons was not observed under basal conditions, in the presence of gap junction “openers” (forskolin, trimethylamine), or after neurons were filled with LY using sharp intracellular microelectrodes. As a “positive control,” dye-coupling was demonstrated in four hippocampal dentate gyrus neurons that were filled using the same patch pipette technique. In addition, none of the tested SNc cells ( n = 12) showed expression of connexin 36 (the “neuronal” connexin) when tested with single-cell RT-PCR. In conclusion, this study revealed extensive rostro-caudal dendritic projections of SNc neurons. Under our in vitro conditions, no evidence was found for dye-coupling among these neurons.

Role of the afterhyperpolarization in control of discharge properties of septal cholinergic neurons in vitro

1996 ◽  
Vol 75 (2) ◽  
pp. 695-706 ◽  
Author(s):  
N. Gorelova ◽  
P. B. Reiner
Keyword(s):  
Choline Acetyltransferase ◽  
Cholinergic Neurons ◽  
Extracellular Calcium ◽  
Spike Frequency ◽  
Membrane Properties ◽  
High Threshold ◽  
Spike Frequency Adaptation ◽  
Frequency Adaptation ◽  
Intrinsic Membrane Properties

1. The properties of the cholinergic neurons of the rat medial septum and nucleus of the diagonal band of Broca (MS/DBB) were studied using whole cell patch-clamp recordings in an in vitro slice preparation. 2. Both the transmitter phenotype and the intrinsic membrane properties of 56 MS/DBB neurons were determined post hoc by visualizing intracellularly deposited biocytin with fluorescent avidin and endogenous choline acetyltransferase with immunofluorescence. Twenty seven of 28 MS/DBB neurons exhibiting both a prominent slow afterhyperpolarization (sAHP) following a single action potential and anomalous rectification were identified as cholinergic. The remaining 28 neurons exhibited other intrinsic membrane properties and none were choline acetyltransferase immunoreactive. 3. The sAHP in MS/DBB cholinergic neurons was blocked reversibly either by reducing extracellular calcium or addition of 100 microM cadmium and irreversibly blocked by 30 nM apamin, suggesting that the sAHP is produced by an apamin-sensitive calcium-activated potassium conductance. 4. MS/DBB cholinergic neurons also exhibited a postspike depolarizing afterpotential (DAP) preceeding the sAHP. Both the DAP and the sAHP were blocked when extracellular calcium was lowered as well as in the presence of 10-50 microM NiCl2. Application of 500 nM omega-conotoxin also reduced the sAHP, while leaving the DAP intact. These data suggest that both transient and high-threshold calcium conductances contribute to generation of the sAHP. 5. When depolarized, cholinergic neurons fired slowly (2-4 Hz) and regularly with little evidence of spike frequency adaptation. When the sAHP was blocked with apamin, the instantaneous frequency of firing increased and the neuron now exhibited prominent spike frequency adaptation. 6. Serotonin (5-HT) reversibly suppressed the sAHP in MS/DBB cholinergic neurons and altered the firing pattern from slow regular discharge to one which exhibited modest spike frequency adaptation. 7. It was concluded that the sAHP limits the firing rate of MS/DBB cholinergic neurons and that physiologically relevant supression of the sAHP by 5-HT may result in state-dependent changes in the discharge pattern of MS/DBB cholinergic neurons.

scholarly journals Conservation of the direct and indirect pathways dichotomy in mouse caudal striatum with uneven distribution of dopamine receptor D1- and D2-expressing neurons

2021 ◽  
Author(s):  
Kumiko Ogata ◽  
Fuko Kadono ◽  
Yasuharu Hirai ◽  
Ken-ichi Inoue ◽  
Masahiko Takada ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Dopamine Receptor ◽  
Common Marmoset ◽  
Projection Neuron ◽  
Membrane Properties ◽  
Electrophysiological Recording ◽  
Projection Neurons ◽  
The Poor ◽  
Neural Tracing

The striatum is one of the key nuclei for adequate control of voluntary behaviors and reinforcement learning. Two striatal projection neuron types, expressing either dopamine receptor D1 (D1R) or dopamine receptor D2 (D2R) constitute two independent output routes: the direct or indirect pathways, respectively. These pathways co-work in balance to achieve coordinated behavior. Two projection neuron types are equivalently intermingled in most striatal space. However, recent studies revealed two atypical zones in the caudal striatum: the zone in which D1R-neurons are the minor population (D1R-poor zone) and that in which D2R-neurons are the minority (D2R-poor zone). It remains obscure as to whether these imbalanced zones have similar properties on axonal projections and electrophysiology to other striatal regions. Based on morphological experiments in mice using immunofluorescence, in situ hybridization, and neural tracing, here, we revealed the poor zones densely projected to the globus pallidus and substantia nigra pars lateralis, with a few collaterals in substantia nigra pars reticulata and compacta. As other striatal regions, D1R-neurons were the direct pathway neurons, while projection neurons in the poor zones possessed similar electrophysiological membrane properties to those in the conventional striatum using in vitro electrophysiological recording. In addition, the poor zones existed irrespective of the age of mice. We also identified the poor zones in the common marmoset as well as other rodents. These results suggest that the poor zones in the caudal striatum follow the conventional projection patterns irrespective of imbalanced distribution of projection neurons. The poor zones could be an innate structure and common in mammals and relate to specific functions via highly restricted projections.

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