NMDA-induced burst firing in a model subthalamic nucleus neuron

2011 ◽  
Vol 106 (2) ◽  
pp. 527-537 ◽  
Author(s):  
Shigeru Kubota ◽  
Jonathan E. Rubin
Keyword(s):  
Subthalamic Nucleus ◽  
Brain Slice ◽  
Experimental Models ◽  
Current Injection ◽  
Burst Firing ◽  
Nucleus Neuron ◽  
Inward Current ◽  
Electrophysiological Recordings ◽  
Rat Brain Slice ◽  
Bursting Activity

Experiments in rat brain slice show that hyperpolarized subthalamic nucleus (STN) neurons engage in slow, regular burst firing when treated with an N-methyl-d-aspartate (NMDA) bath. A depolarization-activated inward current (DIC) has been hypothesized to contribute to this bursting activity. To explore the mechanism for STN burst firing in this setting, we augmented a previously published conductance-based computational model for single rat STN neurons to include both DIC and NMDA currents, fit to data from published electrophysiological recordings. Simulations show that with these additions, the model engages in bursting activity at <1 Hz in response to hyperpolarizing current injection and that this bursting exhibits several features observed experimentally in STN. Furthermore, a reduced model is used to show that the combination of NMDA and DIC currents, but not either alone, suffices to generate oscillations under hyperpolarizing current injection. STN neurons show enhanced burstiness in Parkinson's disease patients and experimental models of parkinsonism, and the burst mechanism studied presently could contribute to this effect.

23. A new adult rat brain slice preparation for ex vivo NMR spectroscopy studies of stroke

1994 ◽  
Vol 52 (1) ◽  
pp. A11
Author(s):  
M.T. Espanol ◽  
L. Litt ◽  
L.-H. Chang ◽  
T.L. James ◽  
P.R. Weinstein ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
Rat Brain ◽  
Brain Slice ◽  
Ex Vivo ◽  
Slice Preparation ◽  
Adult Rat ◽  
Adult Rat Brain ◽  
Spectroscopy Studies ◽  
Rat Brain Slice ◽  
Brain Slice Preparation

Properties of a T-Type Ca2+Channel–Activated Slow Afterhyperpolarization in Thalamic Paraventricular Nucleus and Other Thalamic Midline Neurons

2009 ◽  
Vol 101 (6) ◽  
pp. 2741-2750 ◽  
Author(s):  
Li Zhang ◽  
Leo P. Renaud ◽  
Miloslav Kolaj
Keyword(s):  
Information Transfer ◽  
Brain Slice ◽  
Calcium Concentration ◽  
Channel Blockers ◽  
Thalamic Neurons ◽  
Adrenoceptor Agonist ◽  
Report Data ◽  
Low Threshold ◽  
Rat Brain Slice ◽  
Stimulation Of

Burst firing mediated by a low-threshold spike (LTS) is the hallmark of many thalamic neurons. However, postburst afterhyperpolarizations (AHPs) are relatively uncommon in thalamus. We now report data from patch-clamp recordings in rat brain slice preparations that reveal an LTS-induced slow AHP (sAHP) in thalamic paraventricular (PVT) and other midline neurons, but not in ventrobasal or reticular thalamic neurons. The LTS-induced sAHP lasts 8.9 ± 0.4 s and has a novel pharmacology, with resistance to tetrodotoxin and cadmium and reduction by Ni2+ or nominally zero extracellular calcium concentration, which also attenuate both the LTS and sAHP. The sAHP is inhibited by 10 mM intracellular EGTA or by equimolar replacement of extracellular Ca2+ with Sr2+, consistent with select activation of LVA T-type Ca2+ channels and subsequent Ca2+ influx. In control media, the sAHP reverses near EK+, shifting to −78 mV in 10.1 mM [K+]o and is reduced by Ba2+ or tetraethylammonium. Although these data are consistent with opening of Ca2+-activated K+ channels, this sAHP lacks sensitivity to specific Ca2+-activated K+ channel blockers apamin, iberiotoxin, charybdotoxin, and UCL-2077. The LTS-induced sAHP is suppressed by a β-adrenoceptor agonist isoproterenol, a serotonin 5-HT7 receptor agonist 5-CT, a neuropeptide orexin-A, and by stimulation of the cAMP/protein kinase A pathway with 8-Br-cAMP and forskolin. The data suggest that PVT and certain midline thalamic neurons possess an LTS-induced sAHP that is pharmacologically distinct and may be important for information transfer in thalamic–limbic circuitry during states of attentiveness and motivation.

Acute hypoxia induces elevation of ornithine decarboxylase activity in neonatal rat brain slices

1995 ◽  
Vol 7 (3) ◽  
pp. 385 ◽  
Author(s):  
LD Longo ◽  
S Packianathan
Keyword(s):  
Rat Brain ◽  
Ornithine Decarboxylase ◽  
Bovine Serum ◽  
Brain Slice ◽  
Brain Slices ◽  
Neonatal Rat ◽  
Newborn Rat ◽  
Rat Brain Slice

Recent studies in vivo have demonstrated that ornithine decarboxylase (ODC) activity in the fetal rat brain is elevated 4-5-fold by acute maternal hypoxia. This hypoxic-associated increase is seen in the rat brain in both the newborn and the adult. Because of the intimate involvement of ODC in transcription and translation, as well as in growth and development, it is imperative that the manner in which hypoxia affects the regulation of this enzyme be better understood. In order to achieve this, a brain preparation in vitro was required to eliminate the confounding effects of the dam on the fetal and newborn brain ODC activity in vivo. Therefore, brain slices from 3-4-day-old (P-3) newborn rats were utilized to test the hypothesis that ODC activity increases in response to hypoxia in vitro. Cerebral slices from the P-3 rat pups were allowed to equilibrate and recover in artificial cerebrospinal fluid (ACSF) continuously bubbled with a mixture of 95% O2 and 5% CO2 for 1 h before beginning hypoxic exposures. Higher basal ODC activities were obtained by treating the slices with 0.03% fetal bovine serum (FBS) and 0.003% bovine serum albumin (BSA), rather than with ACSF alone. Hypoxia was induced in the slices by replacing the gas with 40%, 21%, 10%, or 5% O2, all with 5% CO2 and balance N2. With FBS and BSA treatment, ODC activity was maintained at about 0.15-0.11 nM CO2 mg-1 protein h-1 throughout the experiment, which was 2-3-fold higher than that without FBS and BSA. ODC activity increased significantly and peaked between 1 h and 2 h after initiation of hypoxia. For instance, with 21% O2, ODC activity increased approximately 1.5-fold at 1 h and approximately 2-fold at 2 h. These studies demonstrate that: (1) the hypoxic-induced increases observed in vivo in the fetal and newborn rat brain ODC activity can be approximated in a newborn rat brain slice preparation in vitro; (2) newborn rat brain slice preparations may provide an alternative to methods in vivo or cell culture methods for studying the regulation of acute hypoxic-induced enzymes; and (3) high, stable baseline ODC activities in brain slices suggest that the cells in the slice are capable of active metabolism if FBS and BSA are available to mimic conditions in vivo.

Equilibrium Potential of GABAA Current and Implications for Rebound Burst Firing in Rat Subthalamic Neurons In Vitro

2000 ◽  
Vol 83 (5) ◽  
pp. 3169-3172 ◽  
Author(s):  
Mark D. Bevan ◽  
Charles J. Wilson ◽  
J. Paul Bolam ◽  
Peter J. Magill
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Low Frequency ◽  
Burst Firing ◽  
Oscillatory Activity ◽  
Equilibrium Potential ◽  
Oscillatory Mechanism ◽  
Subthalamic Neurons ◽  
Bursting Activity

Reciprocally connected glutamatergic subthalamic and GABAergic globus pallidus neurons have recently been proposed to act as a generator of low-frequency oscillatory activity in Parkinson's disease. To determine whether GABAA receptor-mediated synaptic potentials could theoretically generate rebound burst firing in subthalamic neurons, a feature that is central to the proposed oscillatory mechanism, we determined the equilibrium potential of GABAA current ( E GABAA ) and the degree of hyperpolarization required for rebound firing using perforated-patch recording. In the majority of neurons that fired rebounds, E GABAA was equal to or more hyperpolarized than the hyperpolarization required for rebound burst firing. These data suggest that synchronous activity of pallidal inputs could underlie rhythmic bursting activity of subthalamic neurons in Parkinson's disease.

Suppression of the optical response by lack of glucose in rat brain slice preparations

1998 ◽  
Vol 31 ◽  
pp. S118
Author(s):  
Hiroshi Hasuo ◽  
Shingo Shoji ◽  
Takashi Akasu
Keyword(s):  
Rat Brain ◽  
Brain Slice ◽  
Optical Response ◽  
Rat Brain Slice

Mechanisms of Neuronal Hyperexcitability Caused by Partial Inhibition of Na+-K+-ATPases in the Rat CA1 Hippocampal Region

2002 ◽  
Vol 88 (6) ◽  
pp. 2963-2978 ◽  
Author(s):  
Cyrille Vaillend ◽  
Susanne E. Mason ◽  
Matthew F. Cuttle ◽  
Bradley E. Alger
Keyword(s):  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Burst Firing ◽  
Membrane Properties ◽  
Initial Slope ◽  
Excitatory Postsynaptic Potential ◽  
Neuronal Hyperexcitability ◽  
Partial Inhibition ◽  
Postsynaptic Potential ◽  
Bursting Activity

Extra- and intracellular records were made from rat acute hippocampal slices to examine the effects of partial inhibition of Na+-K+-ATPases (Na+-K+pumps) on neuronal hyperexcitability. Bath application of the low-affinity cardiac glycoside, dihydroouabain (DHO), reversibly induced interictal-like epileptiform bursting activity in the CA1 region. Burst-firing was correlated with inhibition of the pumps, which was assayed by changes in [K+]ouptake rates measured with K+-ion-sensitive microelectrodes. Large increases in resting [K+]odid not occur. DHO induced a transient depolarization (5–6 mV) followed by a long-lasting hyperpolarization (∼6 mV) in CA1 pyramidal neurons, which was accompanied by a 30% decrease in resting input resistance. Block of an electrogenic pump current could explain the depolarization but not the hyperpolarization of the membrane. Increasing [K+]ofrom 3 to 5.5 mM minimized these transient shifts in passive membrane properties without preventing DHO-induced hyperexcitability. DHO decreased synaptic transmission, but increased the coupling between excitatory postsynaptic potentials and spike firing (E-S coupling). Monosynaptic inhibitory postsynaptic potential (IPSP) amplitudes declined to ∼25% of control at the peak of bursting activity; however, miniature TTX-resistant inhibitory postsynaptic current amplitudes were unaffected. DHO also reduced the initial slope of the intracellular excitatory postsynaptic potential (EPSP) to ∼40% of control. The conductances of pharmacologically isolated IPSPs and EPSPs in high-Ca/high-Mg-containing saline were also reduced by DHO by ∼50%. The extracellular fiber volley amplitude was reduced by 15–20%, suggesting that the decrease in neurotransmission was partly due to a reduction in presynaptic fiber excitability. DHO enhanced a late depolarizing potential that was superimposed on the EPSP and could obscure it. This potential was not blocked by antagonists of NMDA receptors, and blockade of NMDA, mGlu, or GABAAreceptors did not affect burst firing. The late depolarizing component enabled the pyramidal cells to reach spike threshold without changing the actual voltage threshold for firing. We conclude that reduced GABAergic potentials and enhanced E-S coupling are the primary mechanisms underlying the hyperexcitability associated with impaired Na+-K+pump activity.

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