Synaptic plasticity in the hippocampal slice: functional consequences

doi:10.1016/0165-0270(94)00188-M

Journal of Neuroscience Methods

Volume 59, Issue 1, June 1995, Pages 11-17

https://doi.org/10.1016/0165-0270(94)00188-M Get rights and content

Abstract

There are 3 known forms of synaptic plasticity at CNS synapses: long-term potentiation (LTP) mediated by NMDA receptor activation, LTP mediated by voltage-dependent calcium channel (VDCC) activation, and long-term depression (LTD) mediated by the NMDA receptor. All 3 forms of synaptic plasticity can be observed in hippocampal CA1 cells, all are induced by afferent activation, all involve Ca²⁺ influx, and all activate Ca²⁺-dependent mechanisms. We consider the functional consequences of the presence of 3, sometime opposing, forms of synaptic plasticity at the same synapse. We suggest that the 2 forms of LTP have different consequences for the synapse. We postulate that the co-existence of potentiating and depressing capabilities influences the network processing capabilities of neural networks.

References (41)

T. Behnisch et al.
Co-activation of metabotropic glutamate and N-methyl-d-aspartate receptors is involved in mechanisms of long-term potentiation maintenance in rat hippocampal CA1 neurons
Neuroscience
(1993)
G. Dechant et al.
Neurotrophin receptors
Prog. Neurobiol.
(1994)
P.A. Dennis et al.
Alpha₂-Macroglobulin is a binding protein for basic fibroblast growth factor
J. Biol. Chem.
(1989)
M. Dragunow et al.
Brain-derived neurotrophic factor after long-term potentiation
Neurosci. Lett.
(1993)
T. Falkenberg et al.
Increased expression of brain-derived neurotrophic factor mRNA in rat hippocampus is associated with improved spatial memory and enriched environment
Neurosci. Lett.
(1992)
P.H. Koo et al.
Monoamine-activated alpha-2-macroglobulin binds trk receptor and inhibits nerve growth factor-stimulated trk phosphorylation and signal transduction
J. Biol. Chem.
(1994)
M. Krug et al.
Anisomycin blocks the late phase of long-term potentiation in the dentate gyrus of freely moving rats
Brain Res. Bull.
(1984)
D.J. Liebl et al.
Comparative binding of neurotrophins (NT-3, CNTF and NGF) and various cytokines to alpha₂-macroglobulin
Biochem. Biophys. Res. Commun.
(1993)
S.O. Meakin et al.
The nerve growth factor family of receptors
Trends Neurosci.
(1992)
R.M. Mulkey et al.
Mechanisms underlying induction of homosynaptic long-term depression in area CA1 of the hippocampus
Neuron
(1992)

S. Otani et al.

Enhancement of extracellular protein concentrations during long-term potentiation in the rat hippocampal slice

Neuroscience

(1992)

D. Van Gool et al.

Alpha₂-macroglobulin expression in neuritic-type plaques in patients with Alzheimer's disease

Neurobio. Aging

(1993)

M. Barbacid

The trk family of neurotrophin receptors

Z.I. Bashir et al.

Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors

Nature

(1993)

M. Baudry et al.

J.E. Black et al.

Developmental approaches to the memory process

I. Cavus et al.

Enhanced neurotrophin receptor expression following long-term potentiation

Soc. Neurosci. Abst.

(1993)

C.M. Coussens et al.

Dendritic localization of LTP and LTD

Soc. Neurosci. Abst.

(1993)

S.M. Dudek et al.

Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-d-aspartate receptor blockade

C. Duffy et al.

Long-term potentiation in the hippocampal slice: evidence for stimulated secretion of newly synthesized proteins

Science

(1981)

Cited by (23)

Short-term environmental enrichment enhances synaptic plasticity in hippocampal slices from aged rats
2016, Neuroscience
Citation Excerpt :
For example, induction of LTP via conventional methods requires activation of N-methyl-d-aspartate receptors (NMDARs). In contrast, induction of LTP with higher frequency stimulation (200–250 Hz) or in the presence of elevated extracellular calcium (Izumi and Zorumski, 1998) involves activation of voltage-dependent calcium channels (VDCCs) (Teyler et al., 1995). Since we were able to induce LTP with conventional methods in EE rats, we hypothesized that the LTP enhanced by EE was NMDAR-dependent.
Age-associated changes in cognition are mirrored by impairments in cellular models of memory and learning, such as long-term potentiation (LTP) and long-term depression (LTD). In young rodents, environmental enrichment (EE) can enhance memory, alter LTP and LTD, as well as reverse cognitive deficits induced by aging. Whether short-term EE can benefit cognition and synaptic plasticity in aged rodents is unclear. Here, we tested if short-term EE could overcome age-associated impairments in induction of LTP and LTD. LTP and LTD could not be induced in the CA1 region of hippocampal slices in control, aged rats using standard stimuli that are highly effective in young rats. However, exposure of aged littermates to EE for three weeks enabled successful induction of LTP and LTD. EE-facilitated LTP was dependent upon N-methyl-d-aspartate receptors (NMDARs). These alterations in synaptic plasticity occurred with elevated levels of phosphorylated cAMP response element-binding protein and vascular endothelial growth factor, but in the absence of changes in several other synaptic and cellular markers. Importantly, our study suggests that even a relatively short period of EE is sufficient to alter synaptic plasticity and molecular markers linked to cognitive function in aged animals.
Automated analysis of intracellular calcium fluorescence in rat organotypic hippocampal cultures: Comparison to a manual, observer based method
2014, Journal of Neuroscience Methods
Citation Excerpt :
Calcium imaging is a pertinent example of this type of microscopy data. The changes in intracellular calcium dynamics in neuronal and non-neuronal cell populations have diverse roles in the maintenance of neuronal homeostasis and the modulation neurotransmission and synaptic plasticity (Teyler et al., 1995; Emptage et al., 2001; Araque and Perea, 2004). At pathophysiological levels, calcium acts as a mediator of excitotoxicity, while acute transient calcium elevations during mild insults may evoke the generation of neuroprotection mechanisms against subsequent insults (Ankarcrona et al., 1995; Kruman and Mattson, 1999; Bickler and Fahlman, 2004; Trendelenburg and Dirnagl, 2005).
The technical advances made in microscopy have been matched by an increase in the application of fluorescent microscopy to answer scientific questions. While analysis of fluorescent microscopy images represents a powerful tool, one must be aware of the potential pitfalls. Frequently, the analysis methods applied involve at least some manual steps which are dependent on an observers input. Typically these steps are laborious and time consuming, but more importantly they are also influenced by an individual observer's bias, drift or imprecision. This raises concerns about the repeatability and definitiveness of the reported observations. Using calcium fluorescence in organotypic hippocampal slices as an experimental platform, we demonstrate the influence that manual interventions can exert on an analysis. We show that there is a high degree of variability between observers, and that this can be sufficient to affect the outcome of an experiment. To counter this, and to eliminate the disagreement between observers, we describe an alternative fully automated method which was created using EBImage package for R. This method has the added advantage of being fully open source and customisable, allowing for this approach to be applied to other analyses.
Continuous blockade of GABA-ergic inhibition induces novel forms of long-lasting plastic changes in apical dendrites of the hippocampal cornu ammonis 1 (CA1) in vitro
2010, Neuroscience
Citation Excerpt :
Control experiments with induction of LTP and previous application of nifedipine alone (without GABA-blockade) did not influence the maintenance of this control-LTP (percent potentiation measured as the field-e.p.s.p. seven hours after LTP induction: controls −168.7±16.3, series with nifedipine −165.2±17.5). These results indicate that conventional L-LTP induced by our stimulation protocol (3 bursts of 100 impulses, 100 Hz) did not require the activation of L-type VDCC, as reported by others (Malenka, 1991; Huber et al., 1995; Teyler et al., 1995; Hanse and Gustafsson, 1995). As mentioned above, the role of VDCC for the late enhancement of excitability after continuous GABA-receptor inhibition could not be investigated after tetanization.
Hippocampal long-term potentiation (LTP) is considered as a fundamental mechanism for learning and memory formation. A role for GABA was reported for the induction and early but not late maintenance of LTP. We have now investigated whether GABA-receptor function is involved in the prolonged maintenance of LTP (>4 h) at afferent synapses at apical dendrites of cornu ammonis 1 (CA1)-pyramidal neurons in hippocampal slices in vitro. Our data demonstrate that GABA-receptor mediated events are not required for conventional, tetanically-induced early- or late-LTP in the hippocampal CA1-region in vitro. Inhibition of GABA-ergic transmission did not negatively influence either early- or late-LTP. In contrast, an additional facilitation was observed at time points corresponding to the establishment of late-LTP (after 3–4 h). Investigation of a second, non-tetanized control input to the same neuronal population revealed that the elevated potentiation of late-LTP in the tetanized input was not LTP-specific. Therefore, we have examined, whether continuous application of GABA-receptor inhibitors also affected the time course of the recorded potentials when a low-frequency stimulation protocol was used. Under these conditions two distinct forms of a late-onset potentiation occurred 5–6 h after drug application. Investigation of mechanisms responsible for this prolonged enhancement of potentials revealed that the higher form of potentiation (potentiation levels above 200%) was dependent on presynaptic activity and N-methyl-d-aspartate (NMDA)-receptor activation, whereas the lower form (potentiation less than 200%) did not require these mechanisms. However, the latter potentiation was prevented by nifedipine, an L-type voltage-dependent calcium channel inhibitor.
DLG3/SAP102 protein expression in malformations of cortical development: A study of human epileptic cortex by tissue microarray
2009, Epilepsy Research
Citation Excerpt :
The N-methyl-D-aspartate (NMDA) receptor is an ionotropic receptor for glutamate, and is thought to be a substrate for cortical hyperexcitability in the brain. The activation of NMDA receptors results in the opening of ion channels which allows the passage of Na+ and K+, and in addition Ca2+, providing the basis for a voltage-dependent current flow through the receptor and playing a critical role in synaptic plasticity (Kirkwood et al., 1993; Teyler et al., 1995). The NMDA receptor is formed by an obligate NR1 subunit and by combinations of NR2A-D subunits (Hollmann and Heinemann, 1994).
The human DLG3 gene encodes the synapse-associated protein 102 (SAP102), which is concentrated in the postsynaptic densities of excitatory synapses and involved in receptor-mediated synaptic transmission via binding to the NR2B subunit of the NMDA receptor. In this study, we investigated the expression and cellular distribution of the DLG3/SAP102 protein in human epileptic cortex. Tissue microarrays of a large number of specimens from patients operated for medically intractable epilepsy were used for immunohistochemical screening with anti-DLG3 antibody. The cellular distribution of the protein was further investigated in samples of malformations of cortical development, and the amount of DLG3 protein in the total homogenate and in the postsynaptic membrane fraction of these samples was quantified by Western blot. We found a strictly neuronal expression of DLG3/SAP102 in epileptogenic cortex as well as in non-epileptic human cortex used for control. In focal cortical dysplasia and tuberous sclerosis complex, the protein was expressed in most neurons including dysplastic neurons, but not in giant cells. Increased expression of DLG3 protein was observed in the postsynaptic membrane fraction of patients with focal cortical dysplasia. Double-labeling experiments confirmed the exclusive neuronal character of the DLG3 expressing cells and the co-localization of the DLG3 protein with the NR2B subunit. Our results suggest a putative role for DLG3/SAP102 in cortical hyperexcitability and epileptogenicity of malformations of cortical development.
17β-estradiol potentiates field excitatory postsynaptic potentials within each subfield of the hippocampus with greatest potentiation of the associational/commissural afferents of CA3
2006, Neuroscience
We sought to determine the impact of 17β-estradiol throughout the hippocampal trisynaptic pathway and to investigate the afferent fiber systems within CA1 and CA3 in detail. To achieve this objective, we utilized multielectrode arrays to simultaneously record the field excitatory postsynaptic potentials from the CA1, dentate gyrus, and CA3 of rat hippocampal slices in the presence or absence of 100 pM 17β-estradiol. We confirmed our earlier findings in CA1, where 17β-estradiol significantly increased field excitatory postsynaptic potentials amplitude (20%±3%) and slope (22%±7%). 17β-Estradiol significantly potentiated the field excitatory postsynaptic potentials in dentate gyrus, amplitude (15%±4%) and slope (17%±5), and in CA3, amplitude (15%±4%) and slope (19%±5%). Using a high-density multielectrode array, we sought to determine the source of potentiation in CA1 and CA3 by determining the impact of 17β-estradiol on the apical afferents and the basal afferents within CA1 and on the mossy fibers and the associational/commissural fibers within CA3. In CA1, 17β-estradiol induced a modest increase in the amplitude (7%±2%) and slope (9%±3%) following apical stimulation with similar magnitude of increase following basal stimulation amplitude (10%±2%) and slope (12%±3%). In CA3, 17β-estradiol augmented the mossy fiber amplitude (15%±3%) and slope (18%±6%) and the associational/commissural fiber amplitude (31%±13%) and slope (40%±15%). These results indicate that 17β-estradiol potentiated synaptic transmission in each subfield of the hippocampal slice, with the greatest magnitude of potentiation at the associational/commissural fibers in CA3. 17β-Estradiol regulation of CA3 responses provides a novel site of 17β-estradiol action that corresponds to the density of estrogen receptors within the hippocampus. The implications of 17β-estradiol potentiation of the field potential in each of the hippocampal subfields and in particular CA3 associational/commissural fibers for memory function and clinical assessment are discussed.
Effect of intermittent hypoxia on long-term potentiation in rat hippocampal slices
2004, Brain Research
Citation Excerpt :
Investigators disagree as to the best approach to measure LTP, i.e. the increase in the population spike amplitude or the increase in the slope of the excitatory postsynaptic potential (EPSP). Nevertheless, although many investigators prefer to use EPSP slope measurements, others [5,17,24] have been using PS amplitude as the monitoring modality of LTP. Moreover, our own experience with the hippocampal slice preparation and its electrophysiology over the past two decades clearly indicates that the population spike amplitude is the most sensitive parameter to changes in environmental conditions.
Intermittent hypoxia (IH) during sleep has been shown to induce apoptosis in a time-dependent manner and spatial learning deficits in adult rats. Recently, we have demonstrated that IH induced significant decreases in Ser-133-phosphorylated cAMP-response element-binding protein (pCREB) without changes in total CREB. The expression of cleaved caspase 3 in the hippocampal CA1, a marker of apoptosis, peaked at 3 days of IH and returned to normoxic values at 14 days of IH. In addition, biphasic changes in spatial task learning were correlated with the CREB phosphorylation time course. In the present study, the rat hippocampal slice preparation was used to evaluate the ability to induce and maintain a CA1 population spike long-term potentiation (PS-LTP) in room air (RA)-maintained and IH-exposed rats. A significant decrease in the ability to sustain PS-LTP for 15 min in slices prepared from IH-exposed rats for either 3 days (34% of total) or 7 days (51% of total) as compared to slices prepared from RA-maintained rats (76% of total) was observed. These results suggest that the diminishment in the ability of neuronal tissue to express and sustain PS-LTP is correlated with previously reported biphasic changes in CREB phosphorylation and programmed cell death.

View all citing articles on Scopus

View full text

Research paperSynaptic plasticity in the hippocampal slice: functional consequences

Abstract

Neuroscience

Prog. Neurobiol.

J. Biol. Chem.

Neurosci. Lett.

Neurosci. Lett.

J. Biol. Chem.

Brain Res. Bull.

Biochem. Biophys. Res. Commun.

Trends Neurosci.

Neuron

Neuroscience

Neurobio. Aging

The trk family of neurotrophin receptors

Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors

Nature

Developmental approaches to the memory process

Enhanced neurotrophin receptor expression following long-term potentiation

Soc. Neurosci. Abst.

Dendritic localization of LTP and LTD

Soc. Neurosci. Abst.

Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-d-aspartate receptor blockade

Long-term potentiation in the hippocampal slice: evidence for stimulated secretion of newly synthesized proteins

Science

Research paper
Synaptic plasticity in the hippocampal slice: functional consequences