scholarly journals Chronic Cortical Injury and Epileptogensis: A Possible Role for Intracellular Chloride Homeostasis

2005 ◽  
Vol 5 (6) ◽  
pp. 239-240 ◽  
Author(s):  
F. Edward Dudek ◽  
Kevin J. Staley
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Adult Rats ◽  
Positive Shift ◽  
Chloride Homeostasis ◽  
Mature Brain ◽  
Significant Difference ◽  
The Difference ◽  
Layer V ◽  
Patch Technique

Impaired Cl– Extrusion in Layer V Pyramidal Neurons of Chronically Injured Epileptogenic Neocortex Jin X, Huguenard JR, Prince DA J Neurophysiol 2005;93:2117–2126 In the mature brain, the K+/Cl– cotransporter KCC2 is important in maintaining low [Cl–]i, resulting in hyperpolarizing GABA responses. Decreases in KCC2 after neuronal injuries result in increases in [Cl–]i and enhanced neuronal excitability due to depolarizing GABA responses. We used the gramicidin perforated-patch technique to measure ECl(∼ EGABA) in layer V pyramidal neurons in slices of partially isolated sensorimotor cortex of adult rats to explore the potential functional consequence of KCC2 downregulation in chronically injured cortex. EGABA was measured by recording currents evoked with brief GABA puffs at various membrane potentials. No significant difference was found in ECl between neurons in control and undercut animals (–71.2 ± 2.6 and −71.8 ± 2.8 mV, respectively). However, when loaded with Cl– by applying muscimol puffs at 0.2 Hz for 60 seconds, neurons in the undercut cortex had a significantly shorter time constant for the positive shift in ECl during the Cl– loading phase (4.3 ± 0.5 s for control and 2.2 ± 0.4 s for undercut; p < 0.01). The positive shift in ECl 3 seconds after the beginning of Cl– loading was also significantly larger in the undercut group than in the control, indicating that neurons in undercut cortex were less effective in maintaining low [Cl–]i during repetitive activation of GABAA receptors. Application of furosemide eliminated the difference between the control and undercut groups for both of these measures of [Cl–]i regulation. The results suggest an impairment in Cl– extrusion resulting from decreased KCC2 expression that may reduce the strength of GABAergic inhibition and contribute to epileptogenesis.

Impaired Cl− Extrusion in Layer V Pyramidal Neurons of Chronically Injured Epileptogenic Neocortex

2005 ◽  
Vol 93 (4) ◽  
pp. 2117-2126 ◽  
Author(s):  
Xiaoming Jin ◽  
John R. Huguenard ◽  
David A. Prince
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Gabaergic Inhibition ◽  
Adult Rats ◽  
Positive Shift ◽  
Mature Brain ◽  
Significant Difference ◽  
The Difference ◽  
Layer V ◽  
Patch Technique

In the mature brain, the K+/Cl− cotransporter KCC2 is important in maintaining low [Cl−]i, resulting in hyperpolarizing GABA responses. Decreases in KCC2 after neuronal injuries result in increases in [Cl−]i and enhanced neuronal excitability due to depolarizing GABA responses. We used the gramicidin perforated-patch technique to measure ECl (∼ EGABA) in layer V pyramidal neurons in slices of partially isolated sensorimotor cortex of adult rats to explore the potential functional consequence of KCC2 downregulation in chronically injured cortex. EGABA was measured by recording currents evoked with brief GABA puffs at various membrane potentials. There was no significant difference in ECl between neurons in control and undercut animals (–71.2 ± 2.6 and –71.8 ± 2.8 mV, respectively). However, when loaded with Cl− by applying muscimol puffs at 0.2 Hz for 60 s, neurons in the undercut cortex had a significantly shorter time constant for the positive shift in ECl during the Cl− loading phase (4.3 ± 0.5 s for control and 2.2 ± 0.4 s for undercut, P < 0.01). The positive shift in ECl 3 s after the beginning of Cl− loading was also significantly larger in the undercut group than in the control, indicating that neurons in undercut cortex were less effective in maintaining low [Cl−]i during repetitive activation of GABAA receptors. Application of furosemide eliminated the difference between the control and undercut groups for both of these measures of [Cl−]i regulation. The results suggest an impairment in Cl− extrusion resulting from decreased KCC2 expression that may reduce the strength of GABAergic inhibition and contribute to epileptogenesis.

Learning-Induced Reversal of the Effect of Noradrenalin on the Postburst AHP

2006 ◽  
Vol 96 (4) ◽  
pp. 1728-1733 ◽  
Author(s):  
Inbar Brosh ◽  
Kobi Rosenblum ◽  
Edi Barkai
Keyword(s):  
Potassium Current ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Piriform Cortex ◽  
Sk Channels ◽  
Similar Extent ◽  
Protein Expression Level ◽  
Calcium Dependent ◽  
The Difference ◽  
Small Conductance

Pyramidal neurons in the piriform cortex from olfactory-discrimination–trained rats have reduced postburst afterhyperpolarization (AHP), for 3 days after learning, and are thus more excitable during this period. Such AHP reduction is caused by decreased conductance of one or more of the calcium-dependent potassium currents, IAHP and s IAHP, that mediate the medium and slow AHPs. In this study, we examined which potassium current is reduced by learning and how the effect of noradrenalin (NE) on neuronal excitability is modified by such reduction. The small conductance (SK) channels inhibitor, apamin, that selectively blocks IAHP, reduced the AHP in neurons from trained, naïve, and pseudotrained rats to a similar extent, thus maintaining the difference in AHP amplitude between neurons from trained rats and controls. In addition, the protein expression level of the SK1, SK2, and SK3 channels was also similar in all groups. NE, which was shown to enhance IAHP while suppressing S IAHP, reduced the AHP in neurons from controls but enhanced the AHP in neurons from trained rats. Our data show that learning-induced enhancement of neuronal excitability is not the result of reduction in the IAHP current. Thus it is probably mediated by reduction in conductance of the other calcium-dependent potassium current, s IAHP. Consequently, the effect of NE on neuronal excitability is reversed. We propose that the change in the effect of NE after learning may act to counterbalance learning-induced hyperexcitability and preserve the piriform cortex ability to subserve olfactory learning.

COUP-TFI/Nr2f1 Orchestrates Intrinsic Neuronal Activity during Development of the Somatosensory Cortex

2020 ◽  
Vol 30 (11) ◽  
pp. 5667-5685 ◽  
Author(s):  
Isabel Del Pino ◽  
Chiara Tocco ◽  
Elia Magrinelli ◽  
Andrea Marcantoni ◽  
Celeste Ferraguto ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Time Windows ◽  
Critical Time ◽  
Network Activity ◽  
Intrinsic Excitability ◽  
Developmental Sequence ◽  
Genetic Mechanisms ◽  
Layer V ◽  
Voltage Gated Ion Channels

Abstract The formation of functional cortical maps in the cerebral cortex results from a timely regulated interaction between intrinsic genetic mechanisms and electrical activity. To understand how transcriptional regulation influences network activity and neuronal excitability within the neocortex, we used mice deficient for Nr2f1 (also known as COUP-TFI), a key determinant of primary somatosensory (S1) area specification during development. We found that the cortical loss of Nr2f1 impacts on spontaneous network activity and synchronization of S1 cortex at perinatal stages. In addition, we observed alterations in the intrinsic excitability and morphological features of layer V pyramidal neurons. Accordingly, we identified distinct voltage-gated ion channels regulated by Nr2f1 that might directly influence intrinsic bioelectrical properties during critical time windows of S1 cortex specification. Altogether, our data suggest a tight link between Nr2f1 and neuronal excitability in the developmental sequence that ultimately sculpts the emergence of cortical network activity within the immature neocortex.

Synaptic Activity in Chronically Injured, Epileptogenic Sensory-Motor Neocortex

2002 ◽  
Vol 88 (1) ◽  
pp. 2-12 ◽  
Author(s):  
Huifang Li ◽  
David A. Prince
Keyword(s):  
Patch Clamp ◽  
Pyramidal Neurons ◽  
Critical Role ◽  
Pyramidal Cells ◽  
Average Frequency ◽  
Synaptic Activity ◽  
Cortical Hyperexcitability ◽  
Significant Difference ◽  
Sensory Motor ◽  
Layer V

We recorded spontaneous and evoked synaptic currents in pyramidal neurons of layer V in chronically injured, epileptogenic neocortex to assess changes in the efficacy of excitatory and inhibitory neurotransmission that might promote cortical hyperexcitability. Partial sensory-motor neocortical isolations with intact blood supply (“undercuts”) were made in 20 rats on postnatal day 21–25 and examined 2–6 wk later in standard brain slice preparations using whole cell patch-clamp techniques. Age-matched, uninjured naive rats ( n = 20) were used as controls. Spontaneous and miniature excitatory and inhibitory postsynaptic currents (s- and mEPSCs; s- and mIPSCs) were recorded using patch-clamp techniques. The average frequency of s- and mEPSCs was significantly higher, while that of s- and mIPSCs was significantly lower in neurons of undercuts versus controls. The increased frequency of excitatory events was due to an increase in both s- and mEPSC frequency, suggesting an increased number of excitatory contacts and/or increased release probability at excitatory terminals. No significant difference was observed in 10–90% rise time of these events. The input-output slopes of fast, short-latency, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate (AMPA/KA) receptor-mediated components of evoked EPSCs were steeper in undercuts than in controls. The peak amplitude of the AMPA/KA component of EPSCs evoked by supra-threshold stimuli was significantly greater in the partially isolated neocortex. In contrast, the N-methyl-d-aspartate receptor-mediated component of evoked EPSCs was not significantly different in neurons of injured versus control cortex, suggesting that the increased AMPA/KA component was due to postsynaptic alterations. Results support the conclusion that layer V pyramidal neurons receive increased AMPA/KA receptor-mediated excitatory synaptic drive and decreased GABAA receptor-mediated inhibition in this chronically injured, epileptogenic cortex. This shift in the balance of excitatory and inhibitory synaptic activation of layer V pyramidal cells toward excitation might be maladaptive and play a critical role in epileptogenesis.

scholarly journals COUP-TFI/Nr2f1 orchestrates intrinsic neuronal activity during cortical area patterning

2019 ◽  
Author(s):  
Isabel del Pino ◽  
Chiara Tocco ◽  
Elia Magrinelli ◽  
Andrea Marcantoni ◽  
Celeste Ferraguto ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Time Windows ◽  
Critical Time ◽  
Network Activity ◽  
Intrinsic Excitability ◽  
Genetic Mechanisms ◽  
Mapping Gene ◽  
Layer V ◽  
Voltage Gated Ion Channels

ABSTRACTThe formation of functional cortical maps in the cerebral cortex results from a timely regulated interaction between intrinsic genetic mechanisms and electrical activity. To understand how transcriptional regulation influences network activity and neuronal excitability within the neocortex, we used mice deficient for the area mapping gene Nr2f1 (also known as COUP-TFI), a key determinant of somatosensory area specification during development. We found that cortical loss of Nr2f1 impacts on spontaneous network activity and synchronization at perinatal stages. In addition, we observed alterations in the intrinsic excitability and morphological features of layer V pyramidal neurons. Accordingly, we identified distinct voltage-gated ion channels regulated by Nr2f1 that might directly influence intrinsic bioelectrical properties during critical time windows of somatosensory cortex specification. Together, our data suggest a tight link between Nr2f1 and neuronal excitability in the developmental sequence that ultimately sculpts the emergence of cortical network activity within the immature neocortex.

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 Refinement of Active and Passive Membrane Properties of Layer V Pyramidal Neurons in Rat Primary Motor Cortex During Postnatal Development

2021 ◽  
Vol 14 ◽  
Author(s):  
Patricia Perez-García ◽  
Ricardo Pardillo-Díaz ◽  
Noelia Geribaldi-Doldán ◽  
Ricardo Gómez-Oliva ◽  
Samuel Domínguez-García ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Postnatal Development ◽  
Primary Motor Cortex ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Membrane Properties ◽  
Neuronal Membrane ◽  
Maturation Process ◽  
Postnatal Maturation ◽  
Layer V

Achieving the distinctive complex behaviors of adult mammals requires the development of a great variety of specialized neural circuits. Although the development of these circuits begins during the embryonic stage, they remain immature at birth, requiring a postnatal maturation process to achieve these complex tasks. Understanding how the neuronal membrane properties and circuits change during development is the first step to understand their transition into efficient ones. Thus, using whole cell patch clamp recordings, we have studied the changes in the electrophysiological properties of layer V pyramidal neurons of the rat primary motor cortex during postnatal development. Among all the parameters studied, only the voltage threshold was established at birth and, although some of the changes occurred mainly during the second postnatal week, other properties such as membrane potential, capacitance, duration of the post-hyperpolarization phase or the maximum firing rate were not defined until the beginning of adulthood. Those modifications lead to a decrease in neuronal excitability and to an increase in the working range in young adult neurons, allowing more sensitive and accurate responses. This maturation process, that involves an increase in neuronal size and changes in ionic conductances, seems to be influenced by the neuronal type and by the task that neurons perform as inferred from the comparison with other pyramidal and motor neuron populations.

Cranial crassicaudiasis in two coastal dolphin species from South Africa is predominantly a disease of immature individuals

2020 ◽  
Vol 139 ◽  
pp. 93-102 ◽  
Author(s):  
MF Van Bressem ◽  
P Duignan ◽  
JA Raga ◽  
K Van Waerebeek ◽  
N Fraijia-Fernández ◽  
...  
Keyword(s):  
South Africa ◽  
Bone Development ◽  
Bottlenose Dolphins ◽  
Fatal Outcome ◽  
Population Level ◽  
Cape Coast ◽  
Osteolytic Lesions ◽  
Immune Mediated ◽  
Significant Difference ◽  
The Difference

Crassicauda spp. (Nematoda) infest the cranial sinuses of several odontocetes, causing diagnostic trabecular osteolytic lesions. We examined skulls of 77 Indian Ocean humpback dolphins Sousa plumbea and 69 Indo-Pacific bottlenose dolphins Tursiops aduncus, caught in bather-protecting nets off KwaZulu-Natal (KZN) from 1970-2017, and skulls of 6 S. plumbea stranded along the southern Cape coast in South Africa from 1963-2002. Prevalence of cranial crassicaudiasis was evaluated according to sex and cranial maturity. Overall, prevalence in S. plumbea and T. aduncus taken off KZN was 13 and 31.9%, respectively. Parasitosis variably affected 1 or more cranial bones (frontal, pterygoid, maxillary and sphenoid). No significant difference was found by gender for either species, allowing sexes to be pooled. However, there was a significant difference in lesion prevalence by age, with immature T. aduncus 4.6 times more likely affected than adults, while for S. plumbea, the difference was 6.5-fold. As severe osteolytic lesions are unlikely to heal without trace, we propose that infection is more likely to have a fatal outcome for immature dolphins, possibly because of incomplete bone development, lower immune competence in clearing parasites or an over-exuberant inflammatory response in concert with parasitic enzymatic erosion. Cranial osteolysis was not observed in mature males (18 S. plumbea, 21 T. aduncus), suggesting potential cohort-linked immune-mediated resistance to infestation. Crassicauda spp. may play a role in the natural mortality of S. plumbea and T. aduncus, but the pathogenesis and population level impact remain unknown.

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