Types Of Long-term Potentiation Research Articles

Effects of uninterrupted sinusoidal LF-EMF stimulation on LTP induced by different combinations of TBS/HFS at the Schaffer collateral-CA1 of synapses

Long-term potentiation (LTP) is an important aspect of synaptic plasticity and is one of the main mechanisms involved in memory. Low-frequency electromagnetic fields (LF-EMFs) such as transcranial magnetic stimulation are emerging neuromodulation tools for the regulation of LTP. However, whether LF-EMFs have different effects on different types of LTP has not yet been verified. Herein, we studied the regulatory effects of 15 Hz/2 mT sinusoidal magnetic field as pre-magnetic stimulation on several types of LTP, which were induced by theta-burst(TBS) or high-frequency stimulation (HFS) or some combination of them, and applied N-methyl-D-aspartate receptor(NMDAR) antagonists to observe the relationship between the regulation of LTP by LF-EMFs and NMDAR in the Schaffer collateral pathway of rat brain slices in vitro. The results presented in this paper are the performance of TBS and HFS was not exactly the same and the recovery speed of TBS-LTP was faster than HFS-LTP after receiving the regulation of LF-EMFs; moreover, the LTP level was affected by the order of combination and the effect of pre-magnetic stimulation could maintain the entire process of the combined induction experiment, while NMDAR antagonists could not completely offset the influence of LF-EMFs. The memory patterns are diverse, and this study has shown LF-EMFs can regulate LTP such as TBS-LTP and HFS-LTP and can continuously affect multiple LTP induction processes. However, different memory processes may have different performance in the face of LF-EMFs regulation. In terms of the mechanism of LF-EMFs-induced LTP regulation, NMDARs may be involved in the process of LF-EMF regulation of LTP, but are not the only factor.

Coexistence of Multiple Types of Synaptic Plasticity in Individual Hippocampal CA1 Pyramidal Neurons.

Understanding learning and memory mechanisms is an important goal in neuroscience. To gain insights into the underlying cellular mechanisms for memory formation, synaptic plasticity processes are studied with various techniques in different brain regions. A valid model to scrutinize different ways to enhance or decrease synaptic transmission is recording of long-term potentiation (LTP) or long-term depression (LTD). At the single cell level, spike timing-dependent plasticity (STDP) protocols have emerged as a powerful tool to investigate synaptic plasticity with stimulation paradigms that also likely occur during memory formation in vivo. Such kind of plasticity can be induced by different STDP paradigms with multiple repeat numbers and stimulation patterns. They subsequently recruit or activate different molecular pathways and neuromodulators for induction and expression of STDP. Dopamine (DA) and brain-derived neurotrophic factor (BDNF) have been recently shown to be important modulators for hippocampal STDP at Schaffer collateral (SC)-CA1 synapses and are activated exclusively by distinguishable STDP paradigms. Distinct types of parallel synaptic plasticity in a given neuron depend on specific subcellular molecular prerequisites. Since the basal and apical dendrites of CA1 pyramidal neurons are known to be heterogeneous, and distance-dependent dendritic gradients for specific receptors and ion channels are described, the dendrites might provide domain specific locations for multiple types of synaptic plasticity in the same neuron. In addition to the distinct signaling and expression mechanisms of various types of LTP and LTD, activation of these different types of plasticity might depend on background brain activity states. In this article, we will discuss some ideas why multiple forms of synaptic plasticity can simultaneously and independently coexist and can contribute so effectively to increasing the efficacy of memory storage and processing capacity of the brain. We hypothesize that resolving the subcellular location of t-LTP and t-LTD mechanisms that are regulated by distinct neuromodulator systems will be essential to reach a more cohesive understanding of synaptic plasticity in memory formation.

The Role of Glutamate Receptors, Synaptic Ion Channels, and Trkb Receptor in Learning and Memory

Introduction: Long-term potentiation (LTP) is a generic term that applies to a form of activity-dependent plasticity that induced by high-frequency or theta burst stimulation and results in enhancement of synaptic transmission. LTP has a key role in learning and memory. Different types of LTP have been observed in distinctive areas of the central nervous system. Hippocampal CA1 area is vital for the formation of long-term memory. Conclusion: Several studies have been shown the importance of signaling pathways in the development of memory and learning. In this review is intended to present an overview of the role of synaptic ion channels, ionotropic and metabotropic glutamate receptors as well as TrkB receptor in LTP formation of learning and memory.

Pre- and postsynaptic localization of NMDA receptor subunits at hippocampal mossy fibre synapses

The N-methyl-d-aspartate (NMDA) type of glutamate receptors is involved in synaptic plasticity in hippocampal mossy fibre-CA3 pyramidal neuron synapses. The ultrastructural localization of NMDA receptor subunits at this synapse type is not known. By postembedding electron microscopic immunogold cytochemistry we show that the NMDA receptor subunits GluN1, GluN2A, GluN2B, GluN2C and GluN2D are located in postsynaptic membranes of mossy fibre as well as CA3 recurrent associational commissural synapses. In the mossy fibres the GluN1, GluN2B and GluN2D labelling patterns suggested that these subunits were located also presynaptically in nerve terminal membranes and in mossy fibre axons. GluN3B was predominantly present in mossy fibre synapses as compared to recurrent associational commissural synapses, showing a presynaptic labelling pattern. In conclusion, while the postsynaptic localization of GluN1, GluN2A, GluN2B, and GluN2D is in good agreement with the recent finding of NMDA receptor-dependent long term potentiation (LTP) at CA3 mossy fibre synapses, we propose that presynaptic GluN1, GluN2B, GluN2D and GluN3B subunits could be involved in plastic phenomena such as certain types of LTP and recurrent mossy fibre growth.

How do climbing fibers teach?

How do climbing fibers teach?

A multi-slice recording system for stable late phase hippocampal long-term potentiation experiments

A major challenge in neuroscience is identifying the cellular and molecular processes underlying learning and memory formation. In the past decades, significant progress has been made in understanding cellular and synaptic mechanisms underlying hippocampal learning and memory using long-term potentiation (LTP) experiments in brain slices as a model system. To expedite LTP measurements it is helpful to further optimize such recording systems. Here, we describe a modification of a multi-slice recording system (SliceMaster, Scientifica Limited, East Sussex, UK) that allows absolutely stable measurements of field excitatory postsynaptic potentials (fEPSPs) for up to 8h in up to eight slices simultaneously. The software Notocord® was used for on-line data acquisition and to control the digital pattern generator which can generate different patterns for slice stimulation, inducing different types of LTP. Moreover, in contrast to common gravity-driven perfusion systems, a Pumped Perfusion System was employed to recycle drug solutions applied to the hippocampal slice. In addition, slices were positioned on two stacked grids for optimal recording of fEPSPs. These two stacked grids were placed in the measuring chambers allowing recordings for several hours without any perturbances. In summary, this modified slice-recording system improves throughput and allows for better statistical design, increases number of used slices per animal and enables very robust LTP measurements for up to 7h. Hence, this system is suitable not only to investigate molecular mechanisms underlying the late phase of LTP, but also to screen candidate compounds in the context of drug discovery.

Octopus Conditioning: A Multi-Armed Approach to the LTP–Learning Question

A recent study shows that avoidance conditioning in the cephalopod Octopus vulgaris is mediated by long-term potentiation (LTP), a form of synaptic plasticity thought to be important in vertebrate associative learning. Thus, LTP appears to be an evolutionarily conserved learning mechanism.

Long-term depression induced by local tetanic stimulation in the rat auditory cortex

In sensory cortices, synaptic plasticities such as long-term potentiation (LTP) and long-term depression (LTD) have important roles in the development of neural circuits and sensory information processing. However, the differential roles and mechanisms of the various types of LTP and LTD are not clear. In the present study, we investigated LTP and two types of LTD in slices obtained from the rat auditory cortex. Supragranular field potentials elicited by layer VI stimulation were recorded through a metal electrode. Transsynaptic field potentials exhibited marked LTP after tetanic stimulation (TS, 100 Hz for 1 s) was applied to layer VI. The same field potential components exhibited LTD after low-frequency stimulation (LFS, 1 Hz for 900 s) was applied to layer VI. LTD of supragranular field potentials was also induced by local TS applied to supragranular layers 0.3 mm from the recording site. Neither LTP nor LTD of either type was induced in the presence of 50 μM d-(−)-2-amino-5-phosphonovalerate (APV), an NMDA receptor antagonist. However, 500 μM (+)-α-methyl-4-carboxyphenylglycine (MCPG), an antagonist of metabotropic glutamate receptors, had no effect. LTD induced by LFS and that induced by local TS were suppressed in the presence of 3 μM bicuculline, an antagonist of GABA A receptors. Each of these forms of LTD occluded the other. These results and intracellular recordings in supragranular pyramidal neurons during LFS and local TS strongly suggest that the two types of LTD share common neural circuits for their induction.

LTP after Stress: Up or Down?

When an organism is exposed to a stressful situation, corticosteroid levels in the brain rise. This rise has consequences for behavioral performance, including memory formation. Over the past decades, it has become clear that a rise in corticosteroid level is also accompanied by a reduction in hippocampal long-term potentiation (LTP). Recent studies, however, indicate that stress does not lead to a universal suppression of LTP. Many factors, including the type of stress, the phase of the stress response, the area of investigation, type of LTP, and the life history of the organism determine in which direction LTP will be changed.

Impaired long‐term memory and long‐term potentiation in N‐type Ca2+channel‐deficient mice

Voltage-dependent N-type Ca(2+) channels, along with the P/Q-type, have a crucial role in controlling the release of neurotransmitters or neuromodulators at presynaptic terminals. However, their role in hippocampus-dependent learning and memory has never been examined. Here, we investigated hippocampus-dependent learning and memory and synaptic plasticity at hippocampal CA3-CA1 synapses in mice deficient for the alpha(1B) subunit of N-type Ca(2+) channels. The mutant mice exhibited impaired learning and memory in the Morris water maze and the social transmission of food preference tasks. In particular, long-term memory was impaired in the mutant mice. Interestingly, among activity-dependent long-lasting synaptic changes, theta burst- or 200-Hz-stimulation-induced long-term potentiation (LTP) was decreased in the mutant, compared with the wild-type mice. This type of LTP is known to require brain-derived neurotrophic factor (BDNF). It was found that both BDNF-induced potentiation of field excitatory postsynaptic potentials and facilitation of the frequency of miniature excitatory postsynaptic currents (mEPSCs) were reduced in the mutant. Taken together, these results demonstrate that N-type Ca(2+) channels are required for hippocampus-dependent learning and memory, and certain forms of LTP.

Subthreshold contribution of N-methyl--aspartate receptors to long-term potentiation induced by low-frequency pairing in rat hippocampal CA1 pyramidal cells

Long-term potentiation (LTP) is a use-dependent and persistent enhancement of synaptic strength. In the CA1 region of the hippocampus, LTP has Hebbian characteristics and requires precisely timed interaction between presynaptic firing and postsynaptic depolarization. Although depolarization is an absolute requirement for plasticity, it is still not clear whether the postsynaptic response during LTP induction should be subthreshold or suprathreshold for the generation of somatic action potential. Here, we use the whole-cell patch-clamp technique and different pairing protocols to examine systematically the postsynaptic induction requirements for LTP. We induce LTP by changes only in membrane potential while keeping the afferent stimulation constant and at minimal levels. This approach permits differentiation of two types of LTP: LTP induced with suprathreshold synaptic responses (LTPAP) and LTP induced with subthreshold excitatory postsynaptic current (EPSCs; LTPEPSC). We found that LTPAP (>40%) required pairing of depolarization (Vm≥−40 mV, for 40–60 s) with four to six (0.1 Hz) single synaptically initiated action potentials. LTPEPSC was of smaller magnitude (<30%) and required pairing of depolarization to −50 mV (60 s) with six subthreshold EPSCs. The N-methyl-d-aspartate receptor (NMDAR) antagonists aminophosphonovaleric acid and 7-chlorokynurenic acid consistently blocked LTPEPSC but were ineffective in preventing LTPAP. Robust, NMDAR-independent LTP is obtained by stronger postsynaptic depolarization that converts the EPSCs to suprathreshold somatic action potentials. Purely NMDAR-dependent LTP is obtained by pairing mild somatic depolarization with subthreshold afferent pulses to the postsynaptic cell. Our results indicate that the degree of postsynaptic depolarization in the presence of single afferent pulses determines the type and magnitude of LTP.

Subthreshold contribution of N-methyl- d-aspartate receptors to long-term potentiation induced by low-frequency pairing in rat hippocampal CA1 pyramidal cells

Long-term potentiation (LTP) is a use-dependent and persistent enhancement of synaptic strength. In the CA1 region of the hippocampus, LTP has Hebbian characteristics and requires precisely timed interaction between presynaptic firing and postsynaptic depolarization. Although depolarization is an absolute requirement for plasticity, it is still not clear whether the postsynaptic response during LTP induction should be subthreshold or suprathreshold for the generation of somatic action potential. Here, we use the whole-cell patch-clamp technique and different pairing protocols to examine systematically the postsynaptic induction requirements for LTP. We induce LTP by changes only in membrane potential while keeping the afferent stimulation constant and at minimal levels. This approach permits differentiation of two types of LTP: LTP induced with suprathreshold synaptic responses (LTP AP) and LTP induced with subthreshold excitatory postsynaptic current (EPSCs; LTP EPSC). We found that LTP AP (>40%) required pairing of depolarization ( V m ≥−40 mV, for 40–60 s) with four to six (0.1 Hz) single synaptically initiated action potentials. LTP EPSC was of smaller magnitude (<30%) and required pairing of depolarization to −50 mV (60 s) with six subthreshold EPSCs. The N-methyl- d-aspartate receptor (NMDAR) antagonists aminophosphonovaleric acid and 7-chlorokynurenic acid consistently blocked LTP EPSC but were ineffective in preventing LTP AP. Robust, NMDAR-independent LTP is obtained by stronger postsynaptic depolarization that converts the EPSCs to suprathreshold somatic action potentials. Purely NMDAR-dependent LTP is obtained by pairing mild somatic depolarization with subthreshold afferent pulses to the postsynaptic cell. Our results indicate that the degree of postsynaptic depolarization in the presence of single afferent pulses determines the type and magnitude of LTP.

Alpha1E-containing Ca2+ channels are involved in synaptic plasticity.

Long-term potentiation (LTP) is the most prominent model for the molecular and cellular mechanisms of learning and memory. Two main forms of LTP have been distinguished. The N-methyl-D-aspartate-receptor-dependent forms of LTP have been studied most extensively, whereas much less is known about N-methyl-D-aspartate-receptor-independent forms of LTP. This latter type of LTP was first described at the mossy fiber synapses in the hippocampus and subsequently at parallel fiber synapses in the cerebellum as well as at corticothalamic synapses. These presynaptic forms of LTP require a rise in the intraterminal calcium concentration, but the channel through which calcium passes has not been identified. By using pharmacological tools as well as genetic deletion, we demonstrate here that alpha1E-containing voltage-dependent calcium channels (VDCCs) shift the threshold for mossy fiber LTP. The channel is not involved in the expression mechanism, but it contributes to the calcium influx during the induction phase. Indeed, optical recordings directly show the presence and the function of alpha1E-containing VDCCs at mossy fiber terminals. Hence, a previously undescribed role for alpha1E-containing VDCCs is suggested by these results.

Rapid eye-movement sleep deprivation does not ‘rescue’ developmentally regulated long-term potentiation in visual cortex of mature rats

The age at which it is possible to obtain a usually age-limited (developmental) form of long-term potentiation (LTP) in rat visual cortex slices can be extended by suppressing rapid eye movement (REM) sleep. In this study, we examined whether REM sleep deprivation can also ‘rescue’ this type of LTP in older rats. Rats, 42–59 days of age, were either REM sleep-deprived for 7–10 days ( n=8), or not deprived of REM sleep (control group, n=8). Brain slices from visual cortex were tested for the developmental form- and a related, non-developmental form of LTP. Three of the eight REM sleep-deprived animals and four of the eight non-deprived animals met criteria for a valid attempt to induce the developmental form of LTP. Though the non-age-regulated form of LTP could be obtained in all seven of these animals, the developmental form could not be elicited in any, indicating that REM sleep deprivation does not uniformly affect all forms of LTP in adult rats. We conclude that extended periods of REM sleep deprivation do not facilitate induction of developmentally regulated LTP once the animal is beyond a certain age.

L-AP3 blocks rises in intracellular calcium associated with hippocampal CA1 LTP.

The involvement of type I metabotropic glutamate receptors in hippocampal CA1 long-term potentiation (LTP) depends on the applied tetanic stimulation protocol. Activation of these receptors may cause an elevation of intracellular calcium via the formation of the second messenger inositol triphosphate (IP3) and subsequent intracellular calcium release. It has been shown that the type I metabotropic receptors antagonist L-2-amino-3-phosphonopropionate (L-AP3) blocks CA1 LTP. Combining dendritic calcium and field potential measurements in CA1 hippocampal area, we found that L-AP3 did not affect single calcium transients but reduced the calcium changes evoked by a single tetanus, preventing the long-lasting calcium enhancements associated with CA1 LTP. These findings suggest that the formation of this type of LTP requires calcium release from IP3-sensitive stores.

NEURONAL MECHANISMS OF MEMORY FORMATION: CONCEPTS OF LONG-TERM POTENTIATION AND BEYOND.: By Christian Holscher. 2001. Cambridge: Cambridge University Press. Price pound65. Pp. 528. ISBN 0-52177-067-X.

The driving force behind this book is the enduring question of whether synaptic plasticity is a suitable model for understanding the basis of learning and memory. In this book synaptic plasticity is taken almost exclusively to mean long-term potentiation (LTP) and there is virtually no discussion of, for example, long-term depression or the cerebellum. The book begins with an introduction by Holscher in which some of the main arguments contained within the rest of the book are rehearsed. This begins with an assessment of the validity of in vitro slice techniques and then questions whether in vitro studies are relevant to learning; whether models of LTP are relevant to learning; and whether knockout techniques and the employment of these are useful for understanding firstly LTP and then learning? This is followed by a critique of the different approaches that have attempted to correlate LTP with the cellular processes that may be involved with learning. Most people in this field will recognize the problems and limitations of the systems that we work with, be these in vivo or in vitro . Most realize that it is not a simple matter to relate synaptic plasticity in a dish or in anaesthetized animals to learning in animals or in humans. Nevertheless, the Introduction is a readable account and provides a useful summary of some of the main issues. The rest of the book is divided into five sections. The first of these deals with `Long-term potentiation in vitro and in vivo '. Abraham discusses the different types of LTP that are found in different brain regions, the types of stimuli usually employed to induce LTP and the underlying mechanisms of induction in different regions. There is an interesting section on neurogenesis (unique …

Immunoelectron microscopic localization of the neural recognition molecules L1, NCAM, and its isoform NCAM180, the NCAM-associated polysialic acid, beta1 integrin and the extracellular matrix molecule tenascin-R in synapses of the adult rat hippocampus.

We have investigated the possibility that morphologically different excitatory glutamatergic synapses of the "trisynaptic circuit" in the adult rodent hippocampus, which display different types of long-term potentiation (LTP), may express the immunoglobulin superfamily recognition molecules L1 and NCAM, the extracellular matrix molecule tenascin-R, and the extracellular matrix receptor constituent beta1 integrin in a differential manner. The neural cell adhesion molecules L1, NCAM (all three major isoforms), NCAM180 (the largest major isoform with the longest cytoplasmic domain), beta1 integrin, polysialic acid (PSA) associated with NCAM, and tenascin-R were localized by pre-embedding immunostaining procedures in the CA3/CA4 region (mossy fiber synapses) and in the dentate gyrus (spine synapses) of the adult rat hippocampus. Synaptic membranes of mossy fiber synapses where LTP is expressed presynaptically did not show detectable levels of immunoreactivity for any of the molecules/epitopes studied. L1, NCAM, and PSA, but not NCAM180 or beta1 integrin, were detectable on axonal membranes of fasciculating mossy fibers. In contrast to mossy fiber synapses, spine synapses in the outer third of the molecular layer of the dentate gyrus, which display postsynaptic expression mechanisms of LTP, were both immunopositive and immunonegative for NCAM, NCAM180, beta1 integrin, and PSA. Those spine synapses postsynaptically immunoreactive for NCAM or PSA also showed immunoreactivity on their presynaptic membranes. NCAM180 was not detectable presynaptically in spine synapses. L1 could not be found in spine synapses either pre- or postsynaptically. Also, the extracellular matrix molecule tenascin-R was not detectable in synaptic clefts of all synapses tested, but was amply present between fasciculating axons, axon-astrocyte contact areas, and astrocytic gap junctions. Differences in expression of the membrane-bound adhesion molecules at both types of synapses may reflect the different mechanisms for induction and/or maintenance of synaptic plasticity.

Critical Role of Presynaptic Nicotinic ACh Receptor in the Formation of Long‐Term Potentiation: Implications for Development of Anti‐Dementia Drugs

Background: Since neuronal nicotinic ACh receptors are involved in the cognitive function, they have been studied as a target of anti‐dementia drugs. The present study was designed to understand the role of nicotinic ACh receptors in the expression of long‐term potentiation (LTP), a cellular model of learning and memory. Methods: The ultrastructural localization of neuronal nicotinic ACh receptors in the rat hippocampus was examined electron‐immunohistochemically using an antibody against the α7 subunit, forming a brain‐type nicotinic ACh receptor. Miniature excitatory postsynaptic currents (mEPSCs) were monitored in cultured rat hippocampal neurons. Schaffer collateral‐CA1 LTP and perforant path LTP were analyzed by recording field excitatory postsynaptic potentials (fEPSPs) and population spikes (PSs) in the CA1 region and the dentate gyrus of rat hippocampal slices or in the intact mouse hippocampus. Results: α7 receptors are preferentially localized on presynaptic terminals, where the receptors are employed in the release of the excitatory neurotransmitter, glutamate. The probability of LTP development was markedly reduced in the presence of the neuronal nicotinic ACh receptor antagonists, α‐bungarotoxin and mecamylamine, in both the CA1 region and the dentate gyrus of rat hippocampal slices. Perforant path LTP was never induced in slices with selective cholinergic denervation using 192 IgG‐saporin, while it was not affected by atropine, a selective muscarinic ACh receptor antagonist, in normal slices. Nicotine facilitated hippocampal neurotransmission with the saturation occluding the potentiation induced by tetanic stimulation, and vice versa. A similar occlusion was also obtained with an intact mouse hippocampus. These types of LTP, which are dependent upon N‐methyl‐D‐aspartate (NMDA) receptors, were still induced by treatment with nicotine in the presence of D‐2‐amino‐5‐phosphonovaleric acid (APV), a selective NMDA receptor antagonist. Conclusion: The results of the present study suggest that presynaptic nicotinic ACh receptors play a critical role as a target of retrograde messengers in the formation of NMDA receptor‐dependent LTP. This may account for the involvement of nicotinic ACh receptors in cognitive function. Drugs enhancing the activity of neuronal nicotinic ACh receptors, therefore, are capable of expressing LTP, conversely, ameliorating dementia.

P42/44 MAP kinase inhibitor PD98059 attenuates multiple forms of synaptic plasticity in rat dentate gyrus in vitro.

The effects of the specific p42/44 mitogen-activated protein (MAP) kinase cascade inhibitor, PD98059, were investigated on three types of long-term potentiation (LTP) in the medial perforant path of the rat dentate gyrus in vitro: LTP induced by 1) high-frequency stimulation (HFS-LTP), 2) application for 10 min of the K+ channel blocker, tetraethylammonium chloride (TEA-LTP), and 3) application of the metabotropic glutamate receptor (mGluR) agonist (S)-dihydrophenylglycine (S-DHPG) for 2 min (DHPG-LTP). Bath perfusion of PD98059 (50 microM) for 1 h inhibited HFS-LTP (111 +/- 5%, mean +/- SE, at 90 min posttetanus in test slices compared with 144 +/- 5% in control slices; n = 6-7). Concentrations of 10 and 20 microM PD98059 had no effect on HFS-LTP (n = 6). PD98059 (50 microM) had no effect on the isolated N-methyl--aspartate excitatory postsynaptic potential (NMDA-EPSP) or on the maintenance phase of HFS-LTP. PD98059 (50 microM) did not affect paired-pulse depression (PPD; interstimulus intervals of 10 and 100 ms) of synaptic transmission as is typically observed in the medial perforant path of the dentate gyrus. Bath application of (S)-DHPG (40 microM) for 2 min gave rise to a potentiation of the EPSPs slope (148 +/- 4% at 1 h post-DHPG wash out; n = 5). Pretreatment of slices with PD98059 (50 microM) inhibited the DHPG-LTP (98 +/- 3% at 1 h post-DHPG wash out; n = 5). The TEA-LTP (125 +/- 4% at 1 h post-TEA wash out; n = 6) was found to be both -2-amino-5-phosphonopentanoic acid (-AP5; 100 microM) and nifedipine (20 microM) independent. However, the T type voltage-dependent calcium-channel blocker, NiCl2 (50 microM), completely inhibited the observed potentiation. The mGluR receptor antagonist alpha-methyl-4-carboxy-phenyl glycine (MCPG; 100 microM) and PD98059 (50 microM) caused a complete block of the TEA-LTP. These data show for the first time an involvement of the p42/44 MAP kinase in the induction and expression of both an NMDA-dependent and two forms of NMDA-independent LTP in the dentate gyrus.

Contributions of AMPA and GABA A receptors to the induction of NMDAR-dependent LTP in CA1

The contributions of (±)-a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and g-aminobutyric acid (GABA A) receptors in the induction of long-term potentiation (LTP) have been studied in the CA1 region of the rat hippocampus. The results suggest that: (1) in physiological conditions, AMPARs are necessary for the induction of N-methyl- d-aspartate receptor (NMDAR)-dependent LTP since LTP cannot be elicited in the presence of the AMPAR antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Although a NMDAR-dependent LTP occurs in the presence of a GABA A antagonist and high concentrations of divalents cations, blockade of AMPARs leads to a voltage-dependent calcium channels (VDCC)-dependent LTP since its induction is blocked by nifedipine and not by APV. (2) The bicarbonate-induced GABA A receptor-mediated depolarizing response is not necessary in the induction of NMDAR-dependent or VDCC-dependent LTP since induction of these two types of LTP were not blocked by acetazolamide or in a nominally bicarbonate-free solution.