scholarly journals Neurophysiological alterations in the nucleus reuniens of a mouse model of Alzheimer’s disease

2019 ◽  
Author(s):  
D.A. Walsh ◽  
J.T. Brown ◽  
A.D. Randall
Keyword(s):  
Mouse Model ◽  
Cortical Neurons ◽  
Transgene Expression ◽  
Membrane Properties ◽  
List Type ◽  
Nucleus Reuniens ◽  
Model Of Alzheimer’S Disease ◽  
Passive Membrane Properties ◽  
Passive Membrane ◽  
Rebound Firing

AbstractTransgenic mice that overproduce beta-amyloid (Aβ) peptides exhibit neurophysiological alterations at the cellular, synaptic and network levels. Recently, increased neuronal activity in nucleus reuniens (Re), has been linked to hyperexcitability within hippocampal-thalamo-cortical networks in the J20 mouse model of amyloidopathy. Here in vitro whole-cell patch clamp recordings were used to compare old pathology-bearing J20 mice and wild-type controls to examine whether alterations to the intrinsic electrophysiological properties of Re neurons could contribute to the amyloidopathy-associated Re hyperactivity. A greater proportion of Re neurons displayed a hyperpolarised membrane potential in J20 mice without changes to the incidence or frequency of spontaneous action potential (AP) generation. Passive membrane properties were independent of transgene expression. Re neurons recorded from J20 mice did not exhibit increased AP generation in response to depolarising current stimuli but did exhibit an increased propensity to rebound burst following hyperpolarising current stimuli. This increase in rebound firing does not appear to result from alterations to T-type calcium channels. Finally, in J20 mice there was an ∼8% reduction in spike width, similar to what we and others have reported in CA1 pyramidal neurons from multiple amyloidopathy mice. We conclude that alterations to the intrinsic properties of Re neurons may contribute to the hyperexcitability observed in hippocampal-thalmo-cortical circuits under pathological Aβ load.Key PointsAlterations in the neurophysiology of hippocampal and cortical neurons has been linked to network hyperexcitability in mouse models of amyloidopathy.The nucleus reuniens (Re) is part of a cognitive network involving the hippocampal formation and prefrontal cortex. Increased cellular activity in Re has been linked to the generation of hippocampal-thalamo-cortical seizure activity in J20 mice.Re neurons display hyperpolarised resting membrane potentials in J20 mice. Passive membrane properties are unaffected by transgene expression. Re neurons recorded from J20 mice did not exhibit increased excitability in response to depolarising current stimuli but did exhibit an increased propensity to rebound burst following hyperpolarising current stimuli. This increased rebound firing was not a result of changes in T-type Ca2+ conductances. Finally we observed a decrease in AP width.These results help us understand how altered Re cellular neurophysiology may contribute to hippocampal-thalamo-cortical hyperexcitability in J20 mice.

scholarly journals Cell Type-Specific Human APP Transgene Expression by Hippocampal Interneurons in the Tg2576 Mouse Model of Alzheimer’s Disease

2019 ◽  
Vol 13 ◽  
Author(s):  
Corinna Höfling ◽  
Emira Shehabi ◽  
Peer-Hendrik Kuhn ◽  
Stefan F. Lichtenthaler ◽  
Maike Hartlage-Rübsamen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Transgene Expression ◽  
Tg2576 Mouse ◽  
Cell Type ◽  
Model Of Alzheimer’S Disease ◽  
Cell Type Specific

Long-Term Alteration of S-Type Potassium Current and Passive Membrane Properties in Aplysia Sensory Neurons Following Axotomy

2002 ◽  
Vol 87 (5) ◽  
pp. 2408-2420 ◽  
Author(s):  
Mark A. Ungless ◽  
Xavier Gasull ◽  
Edgar T. Walters
Keyword(s):  
Leakage Current ◽  
Sensory Neurons ◽  
Outward Current ◽  
The Body ◽  
Membrane Properties ◽  
Resting Membrane Potential ◽  
Current Component ◽  
Passive Membrane Properties ◽  
Passive Membrane

In many neurons, axotomy triggers long-lasting alterations in excitability as well as regenerative growth. We have investigated mechanisms contributing to the expression of axotomy-induced, long-term hyperexcitability (LTH) of mechanosensory neurons in Aplysia californica. Electrophysiological tests were applied to pleural sensory neurons 5–10 days after unilateral crush of pedal nerves. Two-electrode current-clamp experiments revealed that compared with uninjured sensory neurons on the contralateral side of the body, axotomized sensory neurons consistently displayed alterations of passive membrane properties: notably, increases in input resistance ( R in), membrane time constant (τ), and apparent input capacitance. In some cells, axotomy also depolarized the resting membrane potential (RMP). Axotomized sensory neurons showed a lower incidence of voltage relaxation (“sag”) during prolonged hyperpolarizing pulses and greater depolarizations during long (2 s) but not brief (20 ms) pulses. In addition to a reduction in spike accommodation, axotomized sensory neurons displayed a dramatic decrease in current (rheobase) required to reach spike threshold during long depolarizations. The increase in τ was associated with prolongation of responses to brief current pulses and with a large increase in the latency to spike at rheobase. Two-electrode voltage-clamp revealed an axotomy-induced decrease in a current with two components: a leakage current component and a slowly activating, noninactivating outward current component. Neither component was blocked by agents known to block other K+ currents in these neurons. In contrast to the instantaneous leakage current seen with hyperpolarizing and depolarizing steps, the late component of the axotomy-sensitive outward current showed a relatively steep voltage dependence with pulses to V m > −40 mV. These features match those of the S-type (“serotonin-sensitive”) K+ current, I K,S. The close resemblance of I K,S to a background current mediated by TREK-1 (KCNK2) channels in mammals, raises interesting questions about alterations of this family of channels during axotomy-induced LTH in both Aplysia and mammals. The increase in apparent C in may be a consequence of the extensive sprouting that has been observed in axotomized sensory neurons near their somata, and the decrease in I K,S probably helps to compensate for the decrease in excitability that would otherwise occur as new growth causes both cell volume and C in to increase. In peripheral regions of the sensory neuron, a decrease in I K,S might enhance the safety factor for conduction across regenerating segments that are highly susceptible to conduction block.

Perforated patch-clamp analysis of the passive membrane properties of three classes of hippocampal neurons

1992 ◽  
Vol 67 (3) ◽  
pp. 508-529 ◽  
Author(s):  
N. Spruston ◽  
D. Johnston
Keyword(s):  
Membrane Potential ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Physiological Saline ◽  
Membrane Properties ◽  
Resting Potential ◽  
Voltage Dependent ◽  
Perforated Patch Clamp ◽  
Passive Membrane Properties ◽  
Passive Membrane

1. Perforated patch-clamp recordings were made from the three major classes of hippocampal neurons in conventional in vitro slices prepared from adult guinea pigs. This technique provided experimental estimates of passive membrane properties (input resistance, RN, and membrane time constant, tau m) determined in the absence of the leak conductance associated with microelectrode impalement or the washout of cytoplasmic constituents associated with conventional whole-cell recordings. 2. To facilitate comparison of our data with previous results and to determine the passive membrane properties under conditions as physiological as possible, recordings were made at the resting potential, in physiological saline, and without any added blockers of voltage-dependent conductances. 3. Membrane-potential responses to current steps were analyzed, and four criteria were used to identify voltage responses that were the least affected by activation of voltage-dependent conductances. tau m was estimated from the slowest component (tau 0) of multiexponential fits of responses deemed passive by these criteria. RN was estimated from the slope of the linear region in the hyperpolarizing direction of the voltage-current relation. 4. It was not possible to measure purely passive membrane properties that were completely independent of membrane potential in any of the three classes of hippocampal neurons. Changing the membrane potential by constant current injection resulted in changes in RN and tau 0; subthreshold depolarization produced an increase, and hyperpolarization a decrease, in both RN and tau 0 for all three classes of hippocampal neurons. 5. Each of the three classes of hippocampal neurons also displayed a depolarizing "sag" during larger hyperpolarizing voltage transients. To evaluate the effect of the conductances underlying this sag on passive membrane properties, 2-5 mM Cs+ was added to the physiological saline. Extracellular Cs+ effectively blocked the sag in all three classes of hippocampal neurons, but the effect of Cs+ on RN, tau 0, and the voltage dependence of these parameters was unique for each class of neurons. 6. CA1 pyramidal neurons had an RN of 104 +/- 10 (SE) M omega and tau 0 of 28 +/- 2 ms at a resting potential of -64 +/- 2 mV (n = 12). RN and tau 0 were larger at more depolarized potentials in these neurons, but the addition of Cs+ to the physiological saline reversed this voltage dependence. 7. CA3 pyramidal neurons had an RN of 135 +/- 8 M omega and tau 0 of 66 +/- 4 ms at a resting potential of -64 +/- 1 mV (n = 14).(ABSTRACT TRUNCATED AT 400 WORDS)

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