scholarly journals Presynaptic Inhibitory Terminals Are Functionally Abnormal in a Rat Model of Posttraumatic Epilepsy

2010 ◽  
Vol 104 (1) ◽  
pp. 280-290 ◽  
Author(s):  
Leonardo C. Faria ◽  
David A. Prince
Keyword(s):  
Gabaergic Interneurons ◽  
Gabaergic Inhibition ◽  
Input Output ◽  
Paired Pulse ◽  
Posttraumatic Epilepsy ◽  
Pulse Ratio ◽  
Fast Spiking ◽  
Layer V ◽  
Paired Pulse Depression

Partially isolated “undercut” neocortex with intact pial circulation is a well-established model of posttraumatic epileptogenesis. Results of previous experiments showed a decreased frequency of miniature inhibitory postsynaptic currents (mIPSCs) in layer V pyramidal (Pyr) neurons of undercuts. We further examined possible functional abnormalities in GABAergic inhibition in rat epileptogenic neocortical slices in vitro by recording whole cell monosynaptic IPSCs in layer V Pyr cells and fast-spiking (FS) GABAergic interneurons using a paired pulse paradigm. Compared with controls, IPSCs in Pyr neurons of injured slices showed increased threshold and decreased peak amplitude at threshold, decreased input/output slopes, increased failure rates, and a shift from paired pulse depression toward paired pulse facilitation (increased paired pulse ratio or PPR). Increasing [Ca2+]o from 2 to 4 mM partially reversed these abnormalities in Pyr cells of the epileptogenic tissue. IPSCs onto FS cells also had an increased PPR and failures. Blockade of GABAB receptors did not affect the paired results. These findings suggest that there are functional alterations in GABAergic presynaptic terminals onto both Pyr and FS cells in this model of posttraumatic epileptogenesis.

Kinetics of GABAB autoreceptor-mediated suppression of GABA release in rat insular cortex

2012 ◽  
Vol 107 (5) ◽  
pp. 1431-1442 ◽  
Author(s):  
Masayuki Kobayashi ◽  
Hiroki Takei ◽  
Kiyofumi Yamamoto ◽  
Hiroshige Hatanaka ◽  
Noriaki Koshikawa
Keyword(s):  
Insular Cortex ◽  
Pyramidal Cells ◽  
Gaba Release ◽  
Paired Pulse ◽  
Whole Cell Patch Clamp ◽  
Pulse Ratio ◽  
Presynaptic Mechanisms ◽  
Fast Spiking ◽  
Layer V ◽  
Interevent Interval

Release of GABA is controlled by presynaptic GABA receptor type B (GABAB) autoreceptors at GABAergic terminals. However, there is no direct evidence that GABAB autoreceptors are activated by GABA release from their own terminals, and precise profiles of GABAB autoreceptor-mediated suppression of GABA release remain unknown. To explore these issues, we performed multiple whole-cell, patch-clamp recordings from layer V rat insular cortex. Both unitary inhibitory and excitatory postsynaptic currents (uIPSCs and uEPSCs, respectively) were recorded by applying a five-train depolarizing pulse injection at 20 Hz. In connections from both fast-spiking (FS) and non-FS interneurons to pyramidal cells, the GABAB receptor antagonist CGP 52432 had little effect on the initial uIPSC amplitude. However, uIPSCs, responding to later pulses, were effectively facilitated. This CGP 52432-induced facilitation was prominent in the fourth uIPSCs, which were evoked 150 ms after the first uIPSC. The facilitation of uIPSCs was accompanied by an increase in the paired-pulse ratio. In addition, analysis of the coefficient of variation suggests the involvement of presynaptic mechanisms in CGP 52432-induced uIPSC facilitation. Paired-pulse stimulation (interstimulus interval = 150 ms) of presynaptic FS cells revealed that the second uIPSC was also facilitated by CGP 52432, which had little effect on the amplitude and interevent interval of miniature IPSCs. In contrast, uEPSCs, responding to all five stimulations of a presynaptic pyramidal cell, were less affected by CGP 52432. These results suggest that a single presynaptic action potential is sufficient to activate GABAB autoreceptors and to suppress GABA release in the cerebral cortex.

Chronic neocortical epileptogenesis in vitro

1994 ◽  
Vol 71 (5) ◽  
pp. 1762-1773 ◽  
Author(s):  
S. N. Hoffman ◽  
P. A. Salin ◽  
D. A. Prince
Keyword(s):  
White Matter ◽  
Current Source ◽  
Nmda Receptor Antagonist ◽  
White Matter Injury ◽  
Posttraumatic Epilepsy ◽  
Layer V ◽  
Vitro Model ◽  
Interictal Discharges ◽  
Interictal Discharge

1. We used an in vitro model to explore critical aspects of chronic epileptogenesis. Partial neocortical isolations having intact blood supply were made in rat and guinea pig from postnatal day 7 to 34 and then examined 1 to 150 days later in standard brain slice preparations. 2. The epileptogenic potential of several different types of lesions was assessed. Slices containing transcortical (i.e., gray matter) lesions, with or without a contiguous white matter injury (i.e., “undercut”), developed chronic epileptogenesis after a latency of approximately 1–2 wk, manifested by evoked and spontaneous “interictal” discharges and evoked “ictal” events. The region of hyperexcitability did not extend beyond approximately 2 mm from the chronic transcortical lesion and was rarely observed in slices having only an apparent white matter injury. 3. Multiple recordings and current source density (CSD) analysis identified layer V as the source of the interictal discharge. 4. Significant differences in CSD profiles of the evoked interictal discharge occurred between chronically epileptogenic slices and control (noninjured) slices bathed in the convulsant, bicuculline methiodide, suggesting that mechanisms other than disinhibition must be involved in posttraumatic epileptogenesis. 5. Interictal events were blocked in most but not all chronically injured slices by application of the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovalerate (D-AP5), suggesting that non-NMDA receptors were predominantly involved in some preparations. 6. This model of chronic epileptogenesis in vitro will be useful in studies relevant to mechanisms of posttraumatic epilepsy in man.

Dopamine Excites Fast-Spiking Interneurons in the Striatum

2002 ◽  
Vol 87 (4) ◽  
pp. 2190-2194 ◽  
Author(s):  
Enrico Bracci ◽  
Diego Centonze ◽  
Giorgio Bernardi ◽  
Paolo Calabresi
Keyword(s):  
Input Resistance ◽  
Projection Neurons ◽  
Dopamine Receptor Agonist ◽  
Gabaergic Interneurons ◽  
Synaptic Currents ◽  
Cholinergic Interneurons ◽  
Endogenous Dopamine ◽  
Excitatory Action ◽  
Fast Spiking

The striatum is the main recipient of dopaminergic innervation. Striatal projection neurons are controlled by cholinergic and GABAergic interneurons. The effects of dopamine on projection neurons and cholinergic interneurons have been described. Its action on GABAergic interneurons, however, is still unknown. We studied the effects of dopamine on fast-spiking (FS) GABAergic interneurons in vitro, with intracellular recordings. Bath application of dopamine elicited a depolarization accompanied by an increase in membrane input resistance (an effect that persisted in the presence of tetrodotoxin) and action-potential discharge. These effects were mimicked by the D1-like dopamine receptor agonist SKF38393 but not by the D2-like agonist quinpirole. Evoked corticostriatal glutamatergic synaptic currents were not affected by dopamine. Conversely, GABAergic currents evoked by intrastriatal stimulation were reversibly depressed by dopamine and D2-like, but not D1-like, agonists. Cocaine elicited effects similar to those of dopamine on membrane potential and synaptic currents. These results show that endogenous dopamine exerts a dual excitatory action on FS interneurons, by directly depolarizing them (through D1-like receptors) and by reducing their synaptic inhibition (through presynaptic D2-like receptors).

Paired-pulse facilitation of IPSCs in slices of immature and mature mouse somatosensory neocortex

1995 ◽  
Vol 73 (6) ◽  
pp. 2591-2595 ◽  
Author(s):  
I. A. Fleidervish ◽  
M. J. Gutnick
Keyword(s):  
Age Groups ◽  
Equilibrium Potential ◽  
Patch Clamp Technique ◽  
Paired Pulse ◽  
Paired Pulse Facilitation ◽  
Mature Mouse ◽  
Layer V ◽  
Immature Cells ◽  
Whole Cell Recordings ◽  
Paired Pulse Depression

1. Whole cell recordings from layer V neurons of mouse somatosensory cortex were made with the use of a "blind" patch-clamp technique. In slices from immature [postnatal days 6 to 11 (P6-P11)] and juvenile (P18-P21) animals, inhibitory postsynaptic currents (IPSCs) were evoked in all cells by extracellular stimulation at the layer V-VI border. Monosynaptic IPSCs, with latency < 2 ms, were isolated pharmacologically by blockade of ionotropic glutamatergic transmission. IPSCs were blocked by bicuculline methiodide and reversed near the predicted equilibrium potential for Cl-. 2. IPSC characteristics were not different for the two age groups. At 1.5-2 times threshold intensity (0.2 Hz), they fluctuated in amplitude with occasional failures. At -70 or -80 mV, mean amplitudes were -202 +/- 20 (SE) pA and -207 +/- 32 pA for immature (39 cells) and juvenile (13 cells) cortex, respectively. Half rise times were 0.74 +/- 0.03 ms (n = 7 cells) in neonates and 0.67 +/- 0.04 ms (n = 7 cells) in juveniles. Decays were biexponential with tau 1 = 14.8 +/- 1.3 ms and tau 2 = 59.0 +/- 7.4 ms (n = 7 cells) in neonates, and tau 1 = 11.9 +/- 1.1 ms and tau 2 = 55.5 +/- 4.2 ms (n = 7 cells) in juveniles. 3. Pairs of stimuli elicited paired-pulse facilitation (PPF) when delivered at brief interstimulus intervals (ISI), and paired-pulse depression (PPD) at long ISI. PPF, which was evident in 64% of immature cells and 38% of juvenile cells, was maximal (38 +/- 4% greater than the conditioning response) at 20-40 ms. PPD, which was evident in 82% of immature cells and 87% of juvenile cells, was maximal (29 +/- 2% smaller than the conditioning response) by 300 ms. In each age group, some animals showed PPF without PPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence that repetitive seizures in the hippocampus cause a lasting reduction of GABAergic inhibition

1989 ◽  
Vol 61 (2) ◽  
pp. 417-426 ◽  
Author(s):  
J. Kapur ◽  
J. L. Stringer ◽  
E. W. Lothman
Keyword(s):  
Stimulus Intensity ◽  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Interpulse Interval ◽  
Gabaergic Inhibition ◽  
Paired Pulse ◽  
Paired Stimuli ◽  
Ca1 Region ◽  
Quantitative Changes ◽  
Paired Pulse Depression

1. A method was developed to quantify paired-pulse depression of population spikes in the CA1 region of the hippocampus of urethane-anesthetized rats with paired stimuli to the contralateral CA3 region at various states of excitability of pyramidal cells. This method was applied to measure changes following recurrent seizures, a single seizure, or long-term potentiation (LTP). 2. In naive animals paired-pulse depression was highly variable at low stimulus intensities, but constant above a certain "threshold" stimulus intensity. The potency of paired-pulse depression also depended on the time between paired stimuli, being maximal at an interpulse interval of 20 ms. The general relationships of paired-pulse depression to stimulus intensity and to interpulse interval were unaltered after LTP, after a single seizure, and after recurrent seizures, but there were quantitative changes in the last two cases. 3. A variety of pharmacologic agents known to interact with GABAergic inhibition were studied for their effect on paired-pulse depression. These agents affected earlier phases of paired-pulse depression (interpulse intervals less than or equal to 100 ms). The GABA agonist muscimol and the benzodiazepine diazepam enhanced paired-pulse depression whereas the GABA antagonist bicuculline decreased it. 4. Repeated seizures elicited by trains (50-Hz, 10-s durations every 5 min) of electrical stimuli to the hippocampus were associated with progressive lengthening of afterdischarges. 5. Recurrent seizures caused a statistically significant reduction in the potency of earlier phases of paired-pulse depression. There was an increase in the potency of later phases of paired-pulse depression after recurrent seizures, but this was not statistically significant. These changes were present for at least 2 h after the last seizure. 6. An antidromic-orthdromic paired-pulse protocol was used to exclude slow conductance changes as the cause of paired-pulse depression. Paired-pulse depression measured with this method was also decreased by recurrent seizures. 7. A single seizure caused a small reduction in paired-pulse depression that dissipated in less than an hour. 8. A single seizure caused LTP of stimulus intensity versus population spike curves whereas recurrent seizures attenuated or even reversed the potentiation, leading to a rightward shift of the curves relative to control curves. When LTP was produced by a less intense stimulus train (50-Hz, 400-ms duration), there were no associated seizures nor was there any change in paired-pulse depression.(ABSTRACT TRUNCATED AT 400 WORDS)

Dopamine Increases the Gain of the Input-Output Response of Rat Prefrontal Pyramidal Neurons

2008 ◽  
Vol 99 (6) ◽  
pp. 2985-2997 ◽  
Author(s):  
Kay Thurley ◽  
Walter Senn ◽  
Hans-Rudolf Lüscher
Keyword(s):  
Working Memory ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
D1 Receptors ◽  
Input Output ◽  
Prefrontal Cortical ◽  
Noisy Input ◽  
Relationship Of

Dopaminergic modulation of prefrontal cortical activity is known to affect cognitive functions like working memory. Little consensus on the role of dopamine modulation has been achieved, however, in part because quantities directly relating to the neuronal substrate of working memory are difficult to measure. Here we show that dopamine increases the gain of the frequency-current relationship of layer 5 pyramidal neurons in vitro in response to noisy input currents. The gain increase could be attributed to a reduction of the slow afterhyperpolarization by dopamine. Dopamine also increases neuronal excitability by shifting the input-output functions to lower inputs. The modulation of these response properties is mainly mediated by D1 receptors. Integrate-and-fire neurons were fitted to the experimentally recorded input-output functions and recurrently connected in a model network. The gain increase induced by dopamine application facilitated and stabilized persistent activity in this network. The results support the hypothesis that catecholamines increase the neuronal gain and suggest that dopamine improves working memory via gain modulation.

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