scholarly journals The effects of behavioral control over stress on GABAergic spontaneous inhibitory postsynaptic currents in prefrontal cortical pyramidal neurons

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 104
Author(s):  
Juan A Varela ◽  
Jungang Wang ◽  
Donald C Cooper
Keyword(s):  
Pyramidal Neurons ◽  
Deep Layer ◽  
Traumatic Events ◽  
Post Traumatic Stress ◽  
Adult Rats ◽  
Data Set ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Prefrontal Cortical ◽  
Ventral Medial Prefrontal Cortex

Traumatic events may lead to anxiety, depression and post-traumatic stress disorder (PTSD). However, the majority of individuals exposed to trauma do not develop these disorders. The stressor controllability paradigm has been widely used as a model for understanding the neurobiology underlying factors that confer vulnerability and resilience to the outcome of traumatic events. In this paradigm rats receive a series of tail shocks: one group of rats have control over the termination of the shock by means of turning a wheel (escapable shock, ES), while the other “yoked” group of rats receive physically identical shocks but have no control over shock termination (inescapable shock, IS). In subsequent behavioral tests that model components of anxiety and depression, IS rats without control show increased signs of behavioral depression, while ES rats that have control over the shock behave as naïve home caged (HC) rats. We have previously reported that individual deep layer pyramidal neurons from the ventral medial prefrontal cortex (vmPFC) exhibit changes in their intrinsic excitability following ES. To examine if there is a corresponding reduction in synaptic inhibition, we tested IS, ES and HC deep layer pyramidal neurons under identical conditions. Collecting such electrophysiological data from pyramidal neurons after exposure to stress is a technical challenge, yet very useful for conductance-based neural simulations and computational modeling.  Here we present a data set of spontaneous inhibitory postsynaptic currents (sIPSCs) gathered from whole-cell patch-clamp recordings of individual prefrontal cortical deep layer neurons from adult rats (60-70 days old) after exposure to ES, IS or HC. In order to analyze the data, we provide our script used for the detection of synaptic events written for the scientific/engineering program Igor Pro that allows users to define their own event detection parameters.

scholarly journals Homeostatic Plasticity Hypothesis and Mechanisms of Neocortical Epilepsies

2005 ◽  
Vol 5 (4) ◽  
pp. 133-135 ◽  
Author(s):  
Jaideep Kapur ◽  
Stacey Trotter
Keyword(s):  
Synaptic Plasticity ◽  
Neuronal Activity ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Homeostatic Plasticity ◽  
Excitatory Synapses ◽  
Excitatory Postsynaptic Currents ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Homeostatic Synaptic Plasticity

Homeostatic Synaptic Plasticity Can Explain Posttraumatic Epileptogenesis in Chronically Isolated Neocortex Houweling AR, Bazhenov M, Timofeev I, Steriade M, Sejnowski TJ Cereb Cortex 2004 [Epub ahead of print] Permanently isolated neocortex develops chronic hyperexcitability and focal epileptogenesis in a period of days to weeks. The mechanisms operating in this model of posttraumatic epileptogenesis are not well understood. We hypothesized that the spontaneous burst discharges recorded in permanently isolated neocortex result from homeostatic plasticity (a mechanism generally assumed to stabilize neuronal activity) induced by low neuronal activity after deafferentation. To test this hypothesis, we constructed computer models of neocortex incorporating a biologically based homeostatic plasticity rule that operates to maintain firing rates. After deafferentation, homeostatic upregulation of excitatory synapses on pyramidal cells, either with or without concurrent downregulation of inhibitory synapses or upregulation of intrinsic excitability, initiated slowly repeating burst discharges that closely resembled the epileptiform burst discharges recorded in permanently isolated neocortex. These burst discharges lasted a few hundred milliseconds, propagated at 1 to 3 cm/s and consisted of large (10–15 mV) intracellular depolarizations topped by a small number of action potentials. Our results support a role for homeostatic synaptic plasticity as a novel mechanism of posttraumatic epileptogenesis. Excitatory and Inhibitory Postsynaptic Currents in a Rat Model of Epileptogenic Microgyria Jacobs KM, Prince DA J Neurophysiol 2005;93:687–696 Developmental cortical malformations are common in patients with intractable epilepsy; however, mechanisms contributing to this epileptogenesis are currently poorly understood. We previously characterized hyperexcitability in a rat model that mimics the histopathology of human four-layered microgyria. Here we examined inhibitory and excitatory postsynaptic currents in this model to identify functional alterations that might contribute to epileptogenesis associated with microgyria. We recorded isolated whole-cell excitatory postsynaptic currents and GABAA receptor–mediated inhibitory currents from layer V pyramidal neurons in the region previously shown to be epileptogenic (paramicrogyral area) and in homotopic control cortex. Epileptiform-like activity could be evoked in 60% of paramicrogyral (PMG) cells by local stimulation. The peak conductance of both spontaneous and evoked inhibitory postsynaptic currents was significantly larger in all PMG cells compared with controls. This difference in amplitude was not present after blockade of ionotropic glutamatergic currents or for miniature (m) inhibitory postsynaptic currents, suggesting that it was due to the excitatory afferent activity driving inhibitory neurons. This conclusion was supported by the finding that glutamatereceptor antagonist application resulted in a significantly greater reduction in spontaneous inhibitory postsynaptic current frequency in one PMG cell group (PMGE) compared with control cells. The frequency of both spontaneous and miniature excitatory postsynaptic currents was significantly greater in all PMG cells, suggesting that pyramidal neurons adjacent to a microgyrus receive more excitatory input than do those in control cortex. These findings suggest that there is an increase in numbers of functional excitatory synapses on both interneurons and pyramidal cells in the PMG cortex, perhaps due to hyperinnervation by cortical afferents originally destined for the microgyrus proper.

Presynaptic Inactivation of Action Potentials and Postsynaptic Inhibition of GABAA Currents Contribute to KA-Induced Disinhibition in CA1 Pyramidal Neurons

2004 ◽  
Vol 92 (2) ◽  
pp. 873-882 ◽  
Author(s):  
Ning Kang ◽  
Li Jiang ◽  
Wei He ◽  
Jun Xu ◽  
Maiken Nedergaard ◽  
...  
Keyword(s):  
Action Potentials ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Mean Amplitude ◽  
Stratum Radiatum ◽  
Depressant Effect ◽  
Patch Clamp Recording ◽  
Postsynaptic Inhibition ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents

Kainate-type glutamate ionotropic receptors (KAR) mediate either depression or potentiation of inhibitory transmission. The mechanisms underlying the depressant effect of KAR agonists have been controversial. Under dual patch-clamp recording techniques in synaptically coupled pairs of CA1 interneurons and pyramidal neurons in hippocampal slices, micromolar concentrations of KAR agonists, kainic acid (KA, 10 μM) and ATPA (10 μM), induced inactivation of action potentials (APs) in 58 and 50% of presynaptic interneurons, respectively. Inactivation of interneuronal APs might have significantly contributed to KA-induced decreases in evoked inhibitory postsynaptic currents (eIPSCs) that are obtained by stimulating the stratum radiatum. With controlled interneuronal APs, KAR agonists induced a decrease in the potency (mean amplitude of successful events) and mean amplitude (including failures) of unitary inhibitory postsynaptic currents (uIPSCs) without significantly changing the success rate (Ps) at perisomatic high-Ps synapses. In contrast, KAR agonists induced a decrease in both the Ps and potency of uIPSCs at dendritic high-Ps synapses. KAR agonists induced an inhibition of GABAA currents by activating postsynaptic KARs in pyramidal neurons; this was more prominent at dendrites than at soma. Both the exogenous GABA-induced current and the amplitude of miniature IPSCs (mIPSCs) were attenuated by KAR agonists. Thus the postsynaptic KAR-mediated inhibition of GABAA currents may contribute to the KAR agonist-induced decrease in the potency of uIPSCs and KA-induced disinhibition.

scholarly journals Miniature Inhibitory Postsynaptic Currents in CA1 Pyramidal Neurons After Kindling Epileptogenesis

1999 ◽  
Vol 82 (3) ◽  
pp. 1352-1362 ◽  
Author(s):  
Corette J. Wierenga ◽  
Wytse J. Wadman
Keyword(s):  
Pyramidal Neurons ◽  
Single Channel ◽  
Noise Analysis ◽  
Specific Class ◽  
Inhibitory Postsynaptic Currents ◽  
Ca1 Pyramidal Neurons ◽  
Postsynaptic Currents ◽  
Generalized Seizures ◽  
Significant Difference ◽  
The Difference

Miniature inhibitory postsynaptic currents (mIPSCs) were measured in CA1 pyramidal neurons from long-term kindled rats (>6 weeks after they reached the stage of generalized seizures) and compared with controls. A large reduction in the number of mIPSCs was observed in a special group of large mIPSCs (amplitude >75 pA). The frequency of mIPSCs in this group was reduced from 0.042 Hz in controls to 0.027 Hz in the kindled animals. The reduction in this group resulted in a highly significant difference in the amplitude distributions. A distinction was made between fast mIPSCs (rise time <2.8 ms) and slow mIPSCs. Fast mIPSCs, which could originate from synapses onto the soma and proximal dendrites, had significantly larger amplitudes than slow mIPSCs, which could originate from more distal synapses (35.4 ± 1.1 vs. 26.2 ± 0.4 pA in the kindled group; means ± SE). The difference in the value of the mean of all amplitudes and frequency of fast and slow mIPSCs did not reach significance when the kindled group was compared with controls. The mIPSC kinetics were not different after kindling, from which we conclude that the receptor properties had not changed. Nonstationary noise analysis of the largest mIPSCs suggested that the single-channel conductance and the number of postsynaptic receptors was similar in the kindled and control groups. Our results suggest a 40–50% reduction in a small fraction of (peri-) somatic synapses with large or complex postsynaptic structure after kindling. This functionally relevant reduction may be related to previously observed loss of a specific class of interneurons. Our findings are consistent with a reduction in inhibitory drive in the CA1 area. Such a reduction could underlie the enhanced seizure susceptibility after kindling epileptogenesis.

scholarly journals Cannabinoids Depress Inhibitory Synaptic Inputs Received by Layer 2/3 Pyramidal Neurons of the Neocortex

2002 ◽  
Vol 88 (1) ◽  
pp. 534-539 ◽  
Author(s):  
Joseph Trettel ◽  
Eric S. Levine
Keyword(s):  
Pyramidal Neurons ◽  
Cannabinoid Receptor ◽  
Cell Voltage ◽  
Gaba Release ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Presynaptic Site ◽  
Layer 2 ◽  
Kinetics Of

Using whole cell voltage-clamp recordings we investigated the effects of a synthetic cannabinoid (WIN55,212-2) on inhibitory inputs received by layer 2/3 pyramidal neurons in slices of the mouse auditory cortex. Activation of the type 1 cannabinoid receptor (CB1R) with WIN55,212-2 reliably reduced the amplitude of GABAergic inhibitory postsynaptic currents evoked by extracellular stimulation within layer 2/3. The suppression of this inhibition was blocked and reversed by the highly selective CB1R antagonist AM251, confirming a CB1R-mediated inhibition. Pairing evoked inhibitory postsynaptic currents (IPSCs) at short interstimulus intervals while applying WIN55,212-2 resulted in an increase in paired-pulse facilitation suggesting that the probability of GABA release was reduced. A presynaptic site of cannabinoid action was verified by an observed decrease in the frequency with no change in the amplitude or kinetics of action potential–independent postsynaptic currents (mIPSCs). When Cd2+ was added or Ca2+ was omitted from the recording solution, the remaining fraction of Ca2+-independent mIPSCs did not respond to WIN55,212-2. These data suggest that cannabinoids are capable of suppressing the inhibition of neocortical pyramidal neurons by depressing Ca2+-dependent GABA release from local interneurons.

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