TARPs Modulate Receptor-Mediated Paired-Pulse Depression and Recovery from Desensitization

Ouardouz, Mohamed and Jean-Claude Lacaille. Properties of unitary IPSCs in hippocampal pyramidal cells originating from different types of interneurons in young rats. J. Neurophysiol. 77: 1939–1949, 1997. Whole cell recordings were used in hippocampal slices of young rats to examine unitary inhibitory postsynaptic currents (uIPSCs) evoked in CA1 pyramidal cells at room temperature. Loose cell-attached stimulation was applied to activate single interneurons of different subtypes located in stratum oriens (OR), near stratum pyramidale (PYR), and at the border of stratum radiatum and lacunosum-moleculare (LM). uIPSCs evoked by stimulation of PYR and OR interneurons had similar onset latency, rise time, peak amplitude, and decay. In contrast, uIPSCs elicited by activation of LM interneurons were significantly smaller in amplitude and had a slower time course. The mean reversal potential of uIPSCs was −53.1 ± 2.1 (SE) mV during recordings with intracellular solution containing potassium gluconate. With the use of recording solution containing the potassium channel blocker cesium, the reversal potential of uIPSCs was not significantly different (−58.5 ± 2.6 mV), suggesting that these synaptic currents were not mediated by potassium conductances. Bath application of the γ-aminobutyric acid-A (GABAA) receptor antagonist bicuculline (25 μM) reversibly blocked uIPSCs evoked by stimulation of all interneuron subtypes. In bicuculline, the mean peak amplitude of uIPSCs recorded with potassium gluconate was reduced to 3.5 ± 4.4% of control ( n = 7). Similarly, with cesium methanesulfonate, the mean amplitude in bicuculline was 2.9 ± 3.1% of control ( n = 13). Application of the GABAB receptor antagonist CGP 55845A (5 μM) resulted in a significant and reversible increase in the mean amplitude of uIPSCs recorded with cesium-containing intracellular solution. Thus uIPSCs from all cell types appeared under tonic presynaptic inhibition by GABAB receptors. Paired stimulation of individual interneurons at 100- to 200-ms intervals did not result in paired pulse depression of uIPSCs. For individual responses, a significant negative correlation was observed between the amplitude of the first and second uIPSCs. A significant paired pulse facilitation (154.0 ± 8.0%) was observed when the first uIPSC was smaller than the mean of all first uIPSCs. A small, but not significant, paired pulse depression (90.8 ± 4.0%) was found when the first uIPSC was larger than the mean of all first uIPSCs. Our results indicate that these different subtypes of hippocampal interneurons generate Cl−-mediated GABAA uIPSCs. uIPSCs originating from different types of interneurons may have heterogeneous properties and may be subject to tonic presynaptic inhibition via heterosynaptic GABAB receptors. These results suggest a specialization of function for inhibitory interneurons and point to complex presynaptic modulation of interneuron function.

Download Full-text

A Simple Depletion Model of the Readily Releasable Pool of Synaptic Vesicles Cannot Account for Paired-Pulse Depression

Journal of Neurophysiology ◽

10.1152/jn.00554.2006 ◽

2007 ◽

Vol 97 (1) ◽

pp. 948-950 ◽

Cited By ~ 10

Author(s):

Jane M. Sullivan

Keyword(s):

Synaptic Vesicles ◽

Hippocampal Neurons ◽

Synaptic Activity ◽

Excitatory Synapses ◽

Short Term ◽

Paired Pulse ◽

Short Term Plasticity ◽

Releasable Pool ◽

Readily Releasable Pool ◽

Paired Pulse Depression

Paired-pulse depression (PPD) is a form of short-term plasticity that plays a central role in processing of synaptic activity and is manifest as a decrease in the size of the response to the second of two closely timed stimuli. Despite mounting evidence to the contrary, PPD is still commonly thought to reflect depletion of the pool of synaptic vesicles available for release in response to the second stimulus. Here it is shown that PPD cannot be accounted for by depletion at excitatory synapses made by hippocampal neurons because PPD is unaffected by changes in the fraction of the readily releasable pool (RRP) released by the first of a pair of pulses.

Download Full-text

Different Inhibitory Inputs Onto Neostriatal Projection Neurons as Revealed by Field Stimulation

Journal of Neurophysiology ◽

10.1152/jn.00657.2004 ◽

2005 ◽

Vol 93 (2) ◽

pp. 1119-1126 ◽

Cited By ~ 20

Author(s):

Fatuel Tecuapetla ◽

Luis Carrillo-Reid ◽

Jaime N. Guzmán ◽

Elvira Galarraga ◽

José Bargas

Keyword(s):

Channel Blocker ◽

Inhibitory Synapses ◽

Projection Neurons ◽

Medium Spiny Neurons ◽

Field Stimulation ◽

Paired Pulse ◽

Postsynaptic Currents ◽

Spiny Neurons ◽

Short Time ◽

Paired Pulse Depression

This work investigated if diverse properties could be ascribed to evoked inhibitory postsynaptic currents (IPSCs) recorded on rat neostriatal neurons when field stimulation was delivered at two different locations: the globus pallidus (GP) and the neostriatum (NS). Previous work stated that stimulation in the GP could antidromically excite projection axons from medium spiny neurons. This maneuver would predominantly activate the inhibitory synapses that interconnect spiny cells. In contrast, intrastriatal stimulation would preferentially activate inhibitory synapses provided by interneurons. This study shows that, in fact, intensity-amplitude experiments are able to reveal different properties for IPSCs evoked from these two locations (GP and NS). In addition, while all IPSCs evoked from the GP were always sensitive to ω-conotoxin GVIA (CaV2.22.2 or N-channel blocker), one-half of the inhibition evoked from the NS exhibited little sensitivity to ω-conotoxin GVIA. Characteristically, all ω-conotoxin GVIA–insensitive IPSCs exhibited strong paired pulse depression, whereas ω-conotoxin GVIA–sensitive IPSCs evoked from either the GP or the NS could exhibit short-time depression or facilitation. ω-Agatoxin TK (CaV2.12.1+ or P/Q-channel blocker) blocked IPSCs evoked from both locations. Therefore 1) distinct inhibitory inputs onto projection neostriatal cells can be differentially stimulated with field electrodes; 2) N-type Ca2+ channels are not equally expressed in inhibitory terminals activated in the NS; and 3) synapses that interconnect spiny neurons use both N- and P/Q-type Ca2+ channels.

Download Full-text

Paired pulse facilitation is turned into paired pulse depression in hippocampal slices after epilepsy induced by 4-aminopyridine in vivo

Neuropharmacology ◽

10.1016/s0028-3908(02)00024-2 ◽

2002 ◽

Vol 42 (6) ◽

pp. 807-812 ◽

Cited By ~ 21

Author(s):

F. Peña ◽

J. Bargas ◽

R. Tapia

Keyword(s):

Hippocampal Slices ◽

Paired Pulse ◽

Paired Pulse Facilitation ◽

Paired Pulse Depression

Download Full-text

Hippocampal kindling leads to different changes in paired-pulse depression of local evoked field potentials in CA1 area and in fascia dentata

Neuroscience Letters ◽

10.1016/0304-3940(92)90344-7 ◽

1992 ◽

Vol 141 (1) ◽

pp. 101-105 ◽

Cited By ~ 44

Author(s):

Willem Kamphuis ◽

Jan A. Gorter ◽

Wytse J. Wadman ◽

Fernando H.Lopes da Silva

Keyword(s):

Field Potentials ◽

Paired Pulse ◽

Fascia Dentata ◽

Evoked Field Potentials ◽

Ca1 Area ◽

Paired Pulse Depression

Download Full-text

Ontogenesis of Presynaptic GABAB Receptor-Mediated Inhibition in the CA3 Region of the Rat Hippocampus

Journal of Neurophysiology ◽

10.1152/jn.1998.79.3.1341 ◽

1998 ◽

Vol 79 (3) ◽

pp. 1341-1348 ◽

Cited By ~ 23

Author(s):

Olivier Caillard ◽

Heather A. McLean ◽

Yehezkel Ben-Ari ◽

Jean-Luc Gaïarsa

Keyword(s):

Pyramidal Neurons ◽

Gabab Receptor ◽

Hippocampal Slices ◽

Reversal Potential ◽

Rat Hippocampus ◽

Dependent Manner ◽

Paired Pulse ◽

Ca3 Pyramidal Neurons ◽

Paired Pulse Depression ◽

Ca3 Region

Caillard, Olivier, Heather A. McLean, Yehezkel Ben-Ari, and Jean-Luc Gaı̈arsa. Ontogenesis of presynaptic GABAB receptor-mediated inhibition in the CA3 region of the rat hippocampus. J. Neurophysiol. 79: 1341–1348, 1998. γ-Aminobutyric acid-B(GABAB) receptor-dependent and -independent components of paired-pulse depression (PPD) were investigated in the rat CA3 hippocampal region. Intracellular and whole cell recordings of CA3 pyramidal neurons were performed on hippocampal slices obtained from neonatal (5–7 day old) and adult (27–34 day old) rats. Electrical stimulation in the hilus evoked monosynaptic GABAA postsynaptic currents (eIPSCs) isolated in the presence of the ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 μM) and d(−)2-amino-5-phosphovaleric acid (d-AP5, 50 μM) with 2(triethylamino)- N-(2,6-dimethylphenyl) acetamine (QX314) filled electrodes. In adult CA3 pyramidal neurons, when a pair of identical stimuli was applied at interstimulus intervals (ISIs) ranging from 50 to 1,500 ms the amplitude of the second eIPSC was depressed when compared with the first eIPSC. This paired-pulse depression (PPD) was partially blockedb y P - 3 - a m i n o p r o p y l - P - d i e t h o x y m e t h y l p h o s p h o r i c a c i d(CGP35348, 0.5 mM), a selective GABAB receptor antagonist. In neonates, PPD was restricted to ISIs shorter than 200 ms and was not affected by CGP35348. The GABAB receptor agonist baclofen reduced the amplitude of eIPSCs in a dose-dependent manner with the same efficiency in both adults and neonates. Increasing the probability of transmitter release with high Ca2+ (4 mM)/low Mg2+ (0.3 mM) external solution revealed PPD in neonatal CA3 pyramidal neurons that was 1) partially prevented by CGP35348, 2) independent of the membrane holding potential of the recorded cell, and 3) not resulting from a change in the reversal potential of GABAA eIPSCs. In adults the GABA uptake blocker tiagabine (20 μM) increased the duration of eIPSCs and the magnitude of GABAB receptor-dependent PPD. In neonates, tiagabine also increased duration of eIPSCs but to a lesser extent than in adult and did not reveal a GABAB receptor-dependent PPD. These results demonstrate that although GABAB receptor-dependent and -independent mechanisms of presynaptic inhibition are present onGABAergic terminals and functional, they do not operate at the level of monosynaptic GABAergic synaptic transmission at early stages of development. Absence of presynaptic autoinhibition of GABA release seems to be due to the small amount of transmitter that can access presynaptic regulatory sites.

Download Full-text

Pre- and Postnatal Propylthiouracil-Induced Hypothyroidism Impairs Synaptic Transmission and Plasticity in Area CA1 of the Neonatal Rat Hippocampus

Endocrinology ◽

10.1210/en.2003-0395 ◽

2003 ◽

Vol 144 (9) ◽

pp. 4195-4203 ◽

Cited By ~ 87

Author(s):

Li Sui ◽

M. E. Gilbert

Keyword(s):

Thyroid Hormone ◽

Synaptic Transmission ◽

Long Term Potentiation ◽

Synaptic Function ◽

Learning Deficits ◽

Paired Pulse ◽

Area Ca1 ◽

Term Potentiation ◽

Paired Pulse Depression

Abstract Thyroid hormones are essential for neonatal brain development. It is well established that insufficiency of thyroid hormone during critical periods of development can impair cognitive functions. The mechanisms that underlie learning deficits in hypothyroid animals, however, are not well understood. As impairments in synaptic function are likely to contribute to cognitive deficits, the current study tested whether thyroid hormone insufficiency during development would alter quantitative characteristics of synaptic function in the hippocampus. Developing rats were exposed in utero and postnatally to 0, 3, or 10 ppm propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, administered in the drinking water of dams from gestation d 6 until postnatal day (PN) 30. Excitatory postsynaptic potentials and population spikes were recorded from the stratum radiatum and the pyramidal cell layer, respectively, in area CA1 of hippocampal slices from offspring between PN21 and PN30. Baseline synaptic transmission was evaluated by comparing input-output relationships between groups. Paired-pulse facilitation, paired-pulse depression, long-term potentiation, and long-term depression were recorded to examine short- and long-term synaptic plasticity. PTU reduced thyroid hormones, reduced body weight gain, and delayed eye-opening in a dose-dependent manner. Excitatory synaptic transmission was increased by developmental exposure to PTU. Thyroid hormone insufficiency was also dose-dependently associated with a reduction paired-pulse facilitation and long-term potentiation of the excitatory postsynaptic potential and elimination of paired-pulse depression of the population spike. The results indicate that thyroid hormone insufficiency compromises the functional integrity of synaptic communication in area CA1 of developing rat hippocampus and suggest that these changes may contribute to learning deficits associated with developmental hypothyroidism.

Download Full-text