20 research outputs found
Homeostatic maintenance in excitability of tree shrew hippocampal CA3 pyramidal neurons after chronic stress
No full textThe experience of chronic stress induces a reversible regression of hippocampal CA3 apical neuron dendrites. Although such postsynaptic membrane reduction will obviously diminish the possibility of synaptic input, the consequences for the functional membrane properties of these cells are not well understood. We tested the hypothesis that chronic stress affects the input-output characteristics and excitability of CA3 pyramidal cells. Somatic whole-cell current-clamp recording with parallel intracellular biocytin labeling was performed on CA3 neurons from in vitro hippocampal slices from male tree shrews, which were collected after 28 days of psychosocial stress exposure and compared to recordings obtained from control animals. Post hoc morphometric analysis of biocytin-labeled CA3 cells revealed branch regression, by fewer dendritic crossings and length, limited to a distance of similar to280-340 mum from the soma only. The results from whole-cell recording indicate that chronic stress surprisingly reduced the apparent membrane time constant and input resistance 20-25%, accompanied by increased amplitude of the hyperpolarization-induced voltage "sag." All active membrane properties, including depolarization-induced action potential kinetics, complex spiking patterns, and afterhyperpolarization voltages, were indistinguishable from control recordings. Although linear association analysis confirmed that differences in geometry, such as apical length or branch number, were correlated to functional variability in properties of the AP current and voltage threshold, these changes were too marginal to be reflected in the group differences. However, the individual adrenal hormone status was associated significantly with the selective changes in subthreshold excitability. Taken together, the data provide evidence that despite long-term stress induces morphological changes, upregulates cortisol release and shifts the intrinsic membrane properties, the efficacy of somatic excitability of CA3 pyramidal neurons is largely preserved. (C) 2004 Wiley-Liss, Inc
High-voltage-activated Ca2+ currents and the excitability of pyramidal neurons in the hippocampal CA3 subfield in rats depend on corticosterone and time of day
No full textThis study tested the time-of-day dependence of the intrinsic postsynaptic properties of hippocampal CA3 pyramidal neurons. High-voltage-activated Ca2+ currents and the Ca2+- and voltage-dependent afterhyperpolarizations were examined in slices of rat brains obtained at four distinct time periods. Just after onset of the dark phase, the steady-state amplitude of the Ca2+ current (-1.24 ± 0.11 nA) was significantly greater (P < 0.03) than that of the light phase (-0.84 ± 0.06 nA). Over the entire time range, the amplitude of the Ca2+ current correlated with plasma corticosterone levels in a U-shaped function. Furthermore, depolarization-induced excitability during the dark phase exhibited an increased spike after depolarization (3.1 ± 0.1 mV) and a slower adaptation of the firing frequency (146 ± 18%). These findings point to a dynamic time-of-day dependence of the CA3 neuronal properties and postsynaptic Ca2+ currents.
Changes in 5-HT1A and NMDA binding sites by a single rapid transcranial magnetic stimulation procedure in rats
No full textThe effects of a single rapid-rate transcranial magnetic stimulation (rTMS) exposure on neurotransmitter binding sites in the rat brain 24 h after the stimulation were examined. Quantification by in vitro-autoradiography showed no differences for H-3-paroxetine binding (5-HT uptake sites) between rTMS-treated, sham and control animals. In contrast, the number of 5-HT1A binding sites (labeled with H-3-8-OH-DPAT) were selectively increased in the rTMS-group with significantly higher B-MAX values in the frontal cortex, the cingulate cortex, and the anterior olfactory nucleus. A non-specific increase in NMDA binding sites (labeled with I-125-MK-801) in rTMS and sham animals was observed in the hippocampal formation. A selective increase of these binding sites after rTMS was detected in the ventromedial hypothalamus, the basolateral amygdala and layers 5-6 of the parietal cortex. These findings imply that a single rTMS exposure can result in persistent effects on NMDA and 5-HT1A binding sites even 24 h after stimulation and therefore may be of relevance with respect to the therapeutic action of rTMS reported from clinical studies. (C) 1999 Elsevier Science B.V. All rights reserved
Saltatory Conduction along Myelinated Axons Involves a Periaxonal Nanocircuit
No full textThe propagation of electrical impulses along axons is highly accelerated by the myelin sheath and produces saltating or “jumping” action potentials across internodes, from one node of Ranvier to the next. The underlying electrical circuit, as well as the existence and role of submyelin conduction in saltatory conduction remain, however, elusive. Here, we made patch-clamp and high-speed voltage-calibrated optical recordings of potentials across the nodal and internodal axolemma of myelinated neocortical pyramidal axons combined with electron microscopy and experimentally constrained cable modeling. Our results reveal a nanoscale yet conductive periaxonal space, incompletely sealed at the paranodes, which separates the potentials across the low-capacitance myelin sheath and internodal axolemma. The emerging double-cable model reproduces the recorded evolution of voltage waveforms across nodes and internodes, including rapid nodal potentials traveling in advance of attenuated waves in the internodal axolemma, revealing a mechanism for saltation across time and space
Long-term effects of social stress on brain and behavior: a focus on hippocampal functioning
No full textIn order to study mechanisms involved in the etiology of human affective disorders, there is an abundant use of various animal models. Next to genetic factors that predispose for psychopathologies, environmental stress is playing an important role in the etiology of these mental diseases. Since the majority of stress stimuli in humans that lead to psychopathology are of social nature, the study of consequences of social stress in experimental animal models is very valuable. The present review focuses on one of these models that uses the resident-intruder paradigm. In particular the long-lasting effects of social defeat in rats will be evaluated. Data from our laboratory on the consequences of social defeat on emotional behavior, stress responsivity and serotonergic functionality are presented. Furthermore, we will go into detail on hippocampal functioning in socially stressed rats. Very recent results show that there is a differential effect of a brief double social defeat and repetitive social defeat stress on dendritic remodeling in hippocampal CA3 neurons and that this has repercussions on hippocampal LTP and LTD. Both the structural and electrophysiological changes of principal neurons in the hippocampal formation after defeat are discussed as to their relationship with the maintenance in cognitive performance that was observed in socially stressed rats. The results are indicative of a large dynamic range in the adaptive plasticity of the brain, allowing the animals to adapt behaviorally to the previously occurred stressful situation with the progression of time.
First Node of Ranvier Facilitates High-Frequency Burst Encoding
No full textSummaryIn central neurons the first node of Ranvier is located at the first axonal branchpoint, ∼100 μm from the axon initial segment where synaptic inputs are integrated and converted into action potentials (APs). Whether the first node contributes to this signal transformation is not well understood. Here it was found that in neocortical layer 5 axons, the first branchpoint is required for intrinsic high-frequency (≥100 Hz) AP bursts. Furthermore, block of nodal Na+ channels or axotomy of the first node in intrinsically bursting neurons depolarized the somatic AP voltage threshold (∼5 mV) and eliminated APs selectively within a high-frequency cluster in response to steady currents or simulated synaptic inputs. These results indicate that nodal persistent Na+ current exerts an anterograde influence on AP initiation in the axon initial segment, revealing a computational role of the first node of Ranvier beyond conduction of the propagating AP
Signal Processing in the Axon Initial Segment
No full textThe axon initial segment (AIS) is a specialized membrane region in the axon of neurons where action potentials are initiated. Crucial to the function of the AIS is the presence of specific voltage-gated channels clustered at high densities, giving the AIS unique electrical properties. Here we review recent data on the physiology of the AIS. These data indicate that the role of the AIS is far richer than originally thought, leading to the idea that it represents a dynamic signal processing unit within neurons, regulating the integration of synaptic inputs, intrinsic excitability, and transmitter release. Furthermore, these observations point to a critical role of the AIS in disease
Axon Initial Segment Kv1 Channels Control Axonal Action Potential Waveform and Synaptic Efficacy
No full textSummaryAction potentials are binary signals that transmit information via their rate and temporal pattern. In this context, the axon is thought of as a transmission line, devoid of a role in neuronal computation. Here, we show a highly localized role of axonal Kv1 potassium channels in shaping the action potential waveform in the axon initial segment (AIS) of layer 5 pyramidal neurons independent of the soma. Cell-attached recordings revealed a 10-fold increase in Kv1 channel density over the first 50 μm of the AIS. Inactivation of AIS and proximal axonal Kv1 channels, as occurs during slow subthreshold somatodendritic depolarizations, led to a distance-dependent broadening of axonal action potentials, as well as an increase in synaptic strength at proximal axonal terminals. Thus, Kv1 channels are strategically positioned to integrate slow subthreshold signals, providing control of the presynaptic action potential waveform and synaptic coupling in local cortical circuits
Inherited cortical HCN1 channel loss amplifies dendritic calcium electrogenesis and burst firing in a rat absence epilepsy model
No full textRobust adaptive optics for localization microscopy deep in complex tissue
No full textSingle-Molecule Localization Microscopy (SMLM) provides the ability to determine molecular organizations in cells at nanoscale resolution, but in complex biological tissues, where sample-induced aberrations hamper detection and localization, its application remains a challenge. Various adaptive optics approaches have been proposed to overcome these issues, but the exact performance of these methods has not been consistently established. Here we systematically compare the performance of existing methods using both simulations and experiments with standardized samples and find that they often provide limited correction or even introduce additional errors. Careful analysis of the reasons that underlie this limited success enabled us to develop an improved method, termed REALM (Robust and Effective Adaptive Optics in Localization Microscopy), which corrects aberrations of up to 1 rad RMS using 297 frames of blinking molecules to improve single-molecule localization. After its quantitative validation, we demonstrate that REALM enables to resolve the periodic organization of cytoskeletal spectrin of the axon initial segment even at 50 μm depth in brain tissue
