Long-term potentiation (LTP) in the hippocampus is a fundamental process underlying learning and memory in the brain. At CA3-CA1 synapses, three discrete forms of LTP (LTP1, 2, and 3) have been differentiated on the basis of their persistence, maintenance mechanisms, Ca2+ signaling pathways, expression loci, and electrophysiological requirements. We previously showed that LTP2 and LTP3 involve a presynaptic expression component that is established in a translation-dependent manner. Here we investigate the locus of translation required for presynaptic expression. Neurotransmitter release rate was estimated via FM 1-43 destaining from CA3 terminals in hippocampal slices from male Wistar rats (6–8 weeks). Destaining was measured at sites making putative contact with CA1 dendritic processes in stratum radiatum that had been filled with a membrane impermeable translation inhibitor and a fluorescent indicator. Our results suggest that inhibition of postsynaptic translation eliminates the enhanced release ordinarily observed at 160 min post-LTP induction, and that this effect is limited to sites closely apposed to the filled postsynaptic cell. We conclude that postsynaptic translation is required for the presynaptic component of LTP2 and LTP3 expression. These data considerably strengthen the mechanistic separation of LTP1, 2, and 3 and provide evidence for an expanded repertoire of communication between synaptic elements.
LTP; expression; presynaptic; hippocampus; electrophysiology
Cholinergic septohippocampal projections from the medial septal area to the hippocampus are proposed to have important roles in cognition by modulating properties of the hippocampal network. However, the precise spatial and temporal profile of acetylcholine release in the hippocampus remains unclear making it difficult to define specific roles for cholinergic transmission in hippocampal dependent behaviors. This is partly due to a lack of tools enabling specific intervention in, and recording of, cholinergic transmission. Here, we review the organization of septohippocampal cholinergic projections and hippocampal acetylcholine receptors as well as the role of cholinergic transmission in modulating cellular excitability, synaptic plasticity, and rhythmic network oscillations. We point to a number of open questions that remain unanswered and discuss the potential for recently developed techniques to provide a radical reappraisal of the function of cholinergic inputs to the hippocampus.
synaptic plasticity; acetylcholine; medial septum; hippocampus; septohippocampal pathway; memory
The central actions of the hormone leptin in regulating energy homeostasis via the hypothalamus are well documented. However, evidence is growing that this hormone can also modify the structure and function of synapses throughout the CNS. The hippocampus is a region of the forebrain that plays a crucial role in associative learning and memory and is an area also highly vulnerable to neurodegenerative processes. Recent studies indicate that leptin is a potential cognitive enhancer as it modulates the cellular processes underlying hippocampal-dependent learning and memory including dendritic morphology, glutamate receptor trafficking and activity-dependent synaptic plasticity. Here, we review the recent evidence implicating the hormone leptin as a key regulator of hippocampal synaptic function and discuss the role of leptin receptor-driven lipid signaling pathways involved in this process.
leptin; synaptic plasticity; morphology; receptor trafficking; hippocampus; AMPA receptor; PTEN
In terms of its sub-regional differentiation, the hippocampal CA1 region receives cortical information directly via the perforant (temporoammonic) path (pp-CA1 synapse) and indirectly via the tri-synaptic pathway where the last relay station is the Schaffer collateral-CA1 synapse (Sc-CA1 synapse). Research to date on pp-CA1 synapses has been conducted predominantly in vitro and never in awake animals, but these studies hint that information processing at this synapse might be distinct to processing at the Sc-CA1 synapse. Here, we characterized synaptic properties and synaptic plasticity at the pp-CA1 synapse of freely behaving adult rats. We observed that field excitatory postsynaptic potentials at the pp-CA1 synapse have longer onset latencies and a shorter time-to-peak compared to the Sc-CA1 synapse. LTP (>24 h) was successfully evoked by tetanic afferent stimulation of pp-CA1 synapses. Low frequency stimulation evoked synaptic depression at Sc-CA1 synapses, but did not elicit LTD at pp-CA1 synapses unless the Schaffer collateral afferents to the CA1 region had been severed. Paired-pulse responses also showed significant differences. Our data suggest that synaptic plasticity at the pp-CA1 synapse is distinct from the Sc-CA1 synapse and that this may reflect its specific role in hippocampal information processing.
perforant path; synaptic plasticity; hippocampus; CA1; LTD; LTP; in vivo
Adult neurogenesis, restricted to specific regions in the mammalian brain, represents one of the most interesting forms of plasticity in the mature nervous system. Adult-born hippocampal neurons play important roles in certain forms of learning and memory, and altered hippocampal neurogenesis has been associated with a number of neuropsychiatric diseases such as major depression and epilepsy. Newborn neurons go through distinct developmental steps, from a dividing neurogenic precursor to a synaptically integrated mature neuron. Previous studies have uncovered several molecular signaling pathways involved in distinct steps of this maturational process. In this context, the small Rho GTPases, Cdc42, Rac1, and RhoA have recently been shown to regulate the morphological and synaptic maturation of adult-born dentate granule cells in vivo. Distinct upstream regulators, including growth factors that modulate maturation and integration of newborn neurons have been shown to also recruit the small Rho GTPases. Here we review recent findings and highlight the possibility that small Rho GTPases may act as central assimilators, downstream of critical input onto adult-born hippocampal neurons contributing to their maturation and integration into the existing dentate gyrus (DG) circuitry.
neurogenesis; Rac1; Cdc42; RhoA; synaptic integration; spine growth; dendrite; in vivo
Synapses are increasingly recognized as key structures that malfunction in disorders like schizophrenia, mental retardation, and neurodegenerative diseases. The importance and complexity of the synapse has fuelled research into the molecular mechanisms underlying synaptogenesis, synaptic transmission, and plasticity. In this regard, neurotrophic factors such as netrin, Wnt, transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), and others have gained prominence for their ability to regulate synaptic function. Several of these factors were first implicated in neuroprotection, neuronal growth, and axon guidance. However, their roles in synaptic development and function have become increasingly clear, and the downstream signaling pathways employed by these factors have begun to be elucidated. In this review, we will address the role of these factors and their downstream effectors in synaptic function in vivo and in cultured neurons.
netrin; Wnt; TGF-β; TNF-α; synaptogenesis; synaptic transmission and plasticity
We previously reported that the type 2 diabetic Goto–Kakizaki (GK) rats at young adult ages (6–12 weeks) exhibited increased visceral fat mass and hyperleptinemia, due to hyperphagia caused primarily by neuropeptide Y (NPY) overexpression in the hypothalamic arcuate nucleus. Later, we found that GK rats continued to exhibit mesenteric fat accumulation and hyperleptinemia at least until 26 weeks of age, while hyperphagia and NPY overexpression ceased at 15 weeks of age. Therefore, we hypothesized that the long-lasting fat accumulation and hyperleptinemia are due to unidentified brain dysfunction other than NPY overexpression. In GK rats aged 26 weeks, glucose transporter-2 (GLUT2) mRNA expression in ventromedial hypothalamus (VMH) was markedly reduced in parallel with significant decreases in brain-derived neurotrophic factor (BDNF) mRNA level and BDNF-expressing cell numbers in the VMH. Pharmacologic inhibition of glucose utilization reduced BDNF mRNA expression in VMH in vivo and in vitro. The results suggested that impaired glucose utilization caused the reduction of BDNF. On the other hand, intracerebroventricular injection of BDNF for 6 days ameliorated hyperleptinemia in a long-lasting manner concurrently with feeding suppression in GK rats. Restricted feeding paired to BDNF-treated rats reduced plasma leptin level only transiently. BDNF treatment also reduced mesenteric fat mass in GK rats. These results reveal a novel action mode of BDNF to long-lastingly counteract visceral adiposity and hyperleptinemia in addition to and independently of its anorexigenic action. These results suggest that visceral fat accumulation and hyperleptinemia are at least partly due to the reduction of BDNF in VMH primarily caused by impaired glucose utilization in GK rats. The BDNF supplementation could provide an effective treatment of visceral obesity, hyperleptinemia and leptin resistance in type 2 diabetes.
BDNF; type 2 diabetes; adiposity; visceral fat; hyperleptinemia; glucose; VMH
Long-term synaptic plasticity is a major cellular substrate for learning, memory, and behavioral adaptation. Although early examples of long-term synaptic plasticity described a mechanism by which postsynaptic signal transduction was potentiated, it is now apparent that there is a vast array of mechanisms for long-term synaptic plasticity that involve modifications to either or both the presynaptic terminal and postsynaptic site. In this article, we discuss current and evolving approaches to identify presynaptic mechanisms as well as discuss their limitations. We next provide examples of the diverse circuits in which presynaptic forms of long-term synaptic plasticity have been described and discuss the potential contribution this form of plasticity might add to circuit function. Finally, we examine the present evidence for the molecular pathways and cellular events underlying presynaptic long-term synaptic plasticity.
synaptic plasticity; neurotransmitter release; presynaptic plasticity; synaptic vesicle; long-term potentiation; long-term depression
Lipid rafts, cholesterol and lipid rich microdomains, are believed to play important roles as platforms for the partitioning of transmembrane and synaptic proteins involved in synaptic signaling, plasticity, and maintenance. There is increasing evidence of a physical interaction between post-synaptic densities and post-synaptic lipid rafts. Localization of proteins within lipid rafts is highly regulated, and therefore lipid rafts may function as traffic lights modulating and fine-tuning neuronal signaling. The tyrosine kinase neurotrophin receptors (Trk) and the low-affinity p75 neurotrophin receptor (p75NTR) are enriched in neuronal lipid rafts together with the intermediates of downstream signaling pathways, suggesting a possible role of rafts in neurotrophin signaling. Moreover, neurotrophins and their receptors are involved in the regulation of cholesterol metabolism. Cholesterol is an important component of lipid rafts and its depletion leads to gradual loss of synapses, underscoring the importance of lipid rafts for proper neuronal function. Here, we review and discuss the idea that translocation of neurotrophin receptors in synaptic rafts may account for the selectivity of their transduced signals.
neurotrophin signaling; lipid rafts; synaptic rafts; BDNF; TrkB receptor translocation
The dorsoventral axis of the hippocampus is differentiated into dorsal, intermediate, and ventral parts. Whereas the dorsal part is believed to specialize in processing spatial information, the ventral may be equipped to process non-spatial information. The precise role of the intermediate hippocampus is unclear, although recent data suggests it is functionally distinct, at least from the dorsal hippocampus. Learning-facilitated synaptic plasticity describes the ability of hippocampal synapses to respond with robust synaptic plasticity (>24 h) when a spatial learning event is coupled with afferent stimulation that would normally not lead to a lasting plasticity response: in the dorsal hippocampus novel space facilitates robust expression of long-term potentiation (LTP), whereas novel spatial content facilitates long-term depression (LTD). We explored whether the intermediate hippocampus engages in this kind of synaptic plasticity in response to novel spatial experience. In freely moving rats, high-frequency stimulation at 200 Hz (3 bursts of 15 stimuli) elicited synaptic potentiation that lasted for at least 4 h. Coupling of this stimulation with the exploration of a novel holeboard resulted in LTP that lasted for over 24 h. Low frequency afferent stimulation (1 Hz, 900 pulses) resulted in short-term depression (STD) that was significantly enhanced and prolonged by exposure to a novel large orientational (landmark) cues, however LTD was not enabled. Exposure to a holeboard that included novel objects in the holeboard holes elicited a transient enhancement of STD of the population spike (PS) but not field EPSP, and also failed to facilitate the expression of LTD. Our data suggest that the intermediate dentate gyrus engages in processing of spatial information, but is functionally distinct to the dorsal dentate gyrus. This may in turn reflect their assumed different roles in synaptic information processing and memory formation.
LTP; LTD; intermediate hippocampus; dorsoventral axis; in vivo; rats; learning; memory
Chemical synapses are highly specialized cell–cell contacts for communication between neurons in the CNS characterized by complex and dynamic protein networks at both synaptic membranes. The cytomatrix at the active zone (CAZ) organizes the apparatus for the regulated release of transmitters from the presynapse. At the postsynaptic side, the postsynaptic density constitutes the machinery for detection, integration, and transduction of the transmitter signal. Both pre- and postsynaptic protein networks represent the molecular substrates for synaptic plasticity. Their function can be altered both by regulating their composition and by post-translational modification of their components. For a comprehensive understanding of synaptic networks the entire ensemble of synaptic proteins has to be considered. To support this, we established a comprehensive database for synaptic junction proteins (SynProt database) primarily based on proteomics data obtained from biochemical preparations of detergent-resistant synaptic junctions. The database currently contains 2,788 non-redundant entries of rat, mouse, and some human proteins, which mainly have been manually extracted from 12 proteomic studies and annotated for synaptic subcellular localization. Each dataset is completed with manually added information including protein classifiers as well as automatically retrieved and updated information from public databases (UniProt and PubMed). We intend that the database will be used to support modeling of synaptic protein networks and rational experimental design.
chemical synapse; postsynaptic density; synaptic junction; cytomatrix at the active zone; proteomics; rat; mouse; human
The majority of adolescents report to have smoked a cigarette at least once. Adolescence is a critical period of brain development during which maturation of areas involved in cognitive functioning, such as the medial prefrontal cortex (mPFC), is still ongoing. Tobacco smoking during this age may compromise the normal course of prefrontal development and lead to cognitive impairments in later life. In addition, adolescent smokers suffer from attention deficits, which progress with the years of smoking. Recent studies in rodents reveal the molecular changes induced by adolescent nicotine exposure that alter the functioning of synapses in the PFC and underlie the lasting effects on cognitive function. In particular, the expression and function of metabotropic glutamate receptors (mGluRs) are changed and this has an impact on short- and long-term plasticity of glutamatergic synapses in the PFC and ultimately on the attention performance. Here, we review and discuss these recent findings.
adolescence; nicotine; prefrontal cortex; STDP; mGluR; nAChR; cognitive behavior
Fast synaptic inhibition in the brain is mediated by the pre-synaptic release of the neurotransmitter γ-Aminobutyric acid (GABA)and the post-synaptic activation of GABA-sensitive ionotropic receptors. As with excitatory synapses, it is being increasinly appreciated that a variety of plastic processes occur at inhibitory synapses, which operate over a range of timescales. Here we examine a form of activity-dependent plasticity that is somewhat unique to GABAergic transmission. This involves short-lasting changes to the ionic driving force for the post-synaptic receptors, a process referred to as short-term ionic plasticity. These changes are directly related to the history of activity at inhibitory synapses and are influenced by a variety of factors including the location of the synapse and the post-synaptic cell's ion regulation mechanisms. We explore the processes underlying this form of plasticity, when and where it can occur, and how it is likely to impact network activity.
short-term ionic plasticity; GABA; chloride; GABAA receptors; synaptic transmission; EGABA; reversal potential; pH
We studied the role of Homer1 gene products on the presence of synaptic Ca2+-permeable AMPA receptors (AMPARs) and long-term potentiation (LTP) generation in hippocampal CA1 pyramidal neurons, using mice either lacking all Homer1 isoforms (Homer1 KO) or overexpressing the immediate early gene (IEG) product Homer1a (H1aTG). We found that Homer1 KO caused a significant redistribution of the AMPAR subunit GluA2 from the dendritic compartment to the soma. Furthermore, deletion of Homer1 enhanced the AMPAR-mediated component of glutamatergic currents at Schaffer collateral synapses as demonstrated by increased AMPA/NMDA current ratios. Meanwhile, LTP generation appeared to be unaffected. Conversely, sustained overexpression of Homer1a strongly reduced AMPA/NMDA current ratios and polyamine sensitivity of synaptic AMPAR, indicating that the proportion of synaptic GluA2-containing AMPAR increased relative to WT. LTP maintenance was abolished in H1aTG. Notably, overexpression of Homer1a in Homer1 KO or GluA2 KO mice did not affect LTP expression, suggesting activity-dependent interaction between Homer1a and long Homer1 isoforms with GluA2-containing AMPAR. Thus, Homer1a is essential for the activity-dependent regulation of excitatory synaptic transmission.
homer; AMPA receptors; LTP; transgenic mouse models; receptor trafficking
N-cadherin is a calcium-sensitive cell adhesion molecule commonly expressed at synaptic junctions and contributes to formation and maturation of synaptic contacts. This study used heterologous cell cultures of brainstem cholinergic neurons and transfected Chinese Hamster Ovary (CHO) cells to examine whether N-cadherin is sufficient to induce differentiation of cholinergic presynaptic terminals. Brainstem nuclei isolated from transgenic mice expressing enhanced green fluorescent protein (EGFP) under the control of choline acetyltransferase (ChAT) transcriptional regulatory elements (ChATBACEGFP) were cultured as tissue explants for 5 days and cocultured with transfected CHO cells for an additional 2 days. Immunostaining for synaptic vesicle proteins SV2 and synapsin I revealed a ~3-fold increase in the area of SV2 immunolabeling over N-cadherin expressing CHO cells, and this effect was enhanced by coexpression of p120-catenin. Synapsin I immunolabeling per axon length was also increased on N-cadherin expressing CHO cells but required coexpression of p120-catenin. To determine whether N-cadherin induces formation of neurotransmitter release sites, whole-cell voltage-clamp recordings of CHO cells expressing α3 and β4 nicotinic acetylcholine receptor (nAChR) subunits in contact with cholinergic axons were used to monitor excitatory postsynaptic potentials (EPSPs) and miniature EPSPs (mEPSPs). EPSPs and mEPSPs were not detected in both, control and in N-cadherin expressing CHO cells in the absence or presence of tetrodotoxin (TTX). These results indicate that expression of N-cadherin in non-neuronal cells is sufficient to initiate differentiation of presynaptic cholinergic terminals by inducing accumulation of synaptic vesicles; however, development of readily detectable mature cholinergic release sites and/or clustering of postsynaptic nAChR may require expression of additional synaptogenic proteins.
synapse formation; cell adhesion molecules; cadherin; p120-catenin; cholinergic neurons; neuronal nicotinic acetylcholine receptors; synaptogenic proteins; synaptic vesicle clustering
The strength of individual synaptic contacts is considered a key modulator of information flow across circuits. Presynaptically the strength can be parsed into two key parameters: the size of the readily releasable pool (RRP) and the probability that a vesicle in that pool will undergo exocytosis when an action potential fires (Pv). How these variables are controlled and the degree to which they vary across individual nerve terminals is crucial to understand synaptic plasticity within neural circuits. Here we report robust measurements of these parameters in rat hippocampal neurons and their variability across populations of individual synapses. We explore the diversity of presynaptic Ca2+ channel repertoires and evaluate their effect on synaptic strength at single boutons. Finally, we study the degree to which synapses can be differentially modified by a known potentiator of presynaptic function, forskolin. Our experiments revealed that both Pv and RRP spanned a large range, even for synapses made by the same axon, demonstrating that presynaptic efficacy is governed locally at the single synapse level. Synapses varied greatly in their dependence on N or P/Q type Ca2+ channels for neurotransmission, but there was no association between specific channel repertoires and synaptic efficacy. Increasing cAMP concentration using forskolin enhanced synaptic transmission in a Ca2+-independent manner that was inversely related with a synapse's initial Pv, and independent of its RRP size. We propose a simple model based on the relationship between Pv and calcium entry that can account for the variable potentiation of synapses based on initial probability of vesicle fusion.
synapse; exocytosis; release probability; pHluorin; readily releasable pool; imaging
The adrenal chromaffin cell serves as a model system to study fast Ca2+-dependent exocytosis. Membrane capacitance measurements in combination with Ca2+ uncaging offers a temporal resolution in the millisecond range and reveals that catecholamine release occurs in three distinct phases. Release of a readily releasable (RRP) and a slowly releasable (SRP) pool are followed by sustained release, due to maturation, and release of vesicles which were not release-ready at the start of the stimulus. Trains of depolarizations, a more physiological stimulus, induce release from a small immediately releasable pool of vesicles residing adjacent to calcium channels, as well as from the RRP. The SRP is poorly activated by depolarization. A sequential model, in which non-releasable docked vesicles are primed to a slowly releasable state, and then further mature to the readily releasable state, has been proposed. The docked state, dependent on membrane proximity, requires SNAP-25, synaptotagmin, and syntaxin. The ablation or modification of SNAP-25 and syntaxin, components of the SNARE complex, as well as of synaptotagmin, the calcium sensor, and modulators such complexins and Snapin alter the properties and/or magnitudes of different phases of release, and in particular can ablate the RRP. These results indicate that the composition of the SNARE complex and its interaction with modulatory molecules drives priming and provides a molecular basis for different pools of releasable vesicles.
large dense-core vesicles; docking; priming; releasable pools; SNARE complex
Interactions between presynaptic and postsynaptic cellular adhesion molecules (CAMs) drive synapse maturation during development. These trans-synaptic interactions are regulated by alternative splicing of CAM RNAs, which ultimately determines neurotransmitter phenotype. The diverse assortment of RNAs produced by alternative splicing generates countless protein isoforms necessary for guiding specialized cell-to-cell connectivity. Failure to generate the appropriate synaptic adhesion proteins is associated with disrupted glutamatergic and gamma-aminobutyric acid signaling, resulting in loss of activity-dependent neuronal plasticity, and risk for developmental disorders, including autism. While the majority of genetic mutations currently linked to autism are rare variants that change the protein-coding sequence of synaptic candidate genes, regulatory polymorphisms affecting constitutive and alternative splicing have emerged as risk factors in numerous other diseases, accounting for an estimated 40–60% of general disease risk. Here, we review the relationship between aberrant RNA splicing of synapse-related genes and autism spectrum disorders.
autism spectrum disorder; synaptogenesis; alternative RNA splicing; cellular adhesion molecules; neurexin; neuroligin; gene expression; neural development
Filamentous tau inclusions are hallmarks of Alzheimer's disease and related neurodegenerative tauopathies, but the molecular mechanisms involved in tau-mediated changes in neuronal function and their possible effects on synaptic transmission are unknown. We have evaluated the effects of human tau protein injected directly into the presynaptic terminal axon of the squid giant synapse, which affords functional, structural, and biochemical analysis of its action on the synaptic release process. Indeed, we have found that at physiological concentration recombinant human tau (h-tau42) becomes phosphorylated, produces a rapid synaptic transmission block, and induces the formation of clusters of aggregated synaptic vesicles in the vicinity of the active zone. Presynaptic voltage clamp recordings demonstrate that h-tau42 does not modify the presynaptic calcium current amplitude or kinetics. Analysis of synaptic noise at the post-synaptic axon following presynaptic h-tau42 microinjection revealed an initial phase of increase spontaneous transmitter release followed by a marked reduction in noise. Finally, systemic administration of T-817MA, a proposed neuro-protective agent, rescued tau-induced synaptic abnormalities. Our results show novel mechanisms of h-tau42 mediated synaptic transmission failure and identify a potential therapeutic agent to treat tau-related neurotoxicity.
tauopathies; synaptic transmission; hyperphosphorylation; Altzheimer's disease; neurodegenerative; human tau; synaptic vesicles; neuro-protective agent
How learning and memory is achieved in the brain is a central question in neuroscience. Key to today’s research into information storage in the brain is the concept of synaptic plasticity, a notion that has been heavily influenced by Hebb's (1949) postulate. Hebb conjectured that repeatedly and persistently co-active cells should increase connective strength among populations of interconnected neurons as a means of storing a memory trace, also known as an engram. Hebb certainly was not the first to make such a conjecture, as we show in this history. Nevertheless, literally thousands of studies into the classical frequency-dependent paradigm of cellular learning rules were directly inspired by the Hebbian postulate. But in more recent years, a novel concept in cellular learning has emerged, where temporal order instead of frequency is emphasized. This new learning paradigm – known as spike-timing-dependent plasticity (STDP) – has rapidly gained tremendous interest, perhaps because of its combination of elegant simplicity, biological plausibility, and computational power. But what are the roots of today’s STDP concept? Here, we discuss several centuries of diverse thinking, beginning with philosophers such as Aristotle, Locke, and Ribot, traversing, e.g., Lugaro’s plasticità and Rosenblatt’s perceptron, and culminating with the discovery of STDP. We highlight interactions between theoretical and experimental fields, showing how discoveries sometimes occurred in parallel, seemingly without much knowledge of the other field, and sometimes via concrete back-and-forth communication. We point out where the future directions may lie, which includes interneuron STDP, the functional impact of STDP, its mechanisms and its neuromodulatory regulation, and the linking of STDP to the developmental formation and continuous plasticity of neuronal networks.
synaptic plasticity; spike-timing-dependent plasticity; bidirectional plasticity; long term depression; long term plasticity; history; learning; memory
Spike timing-dependent plasticity (STDP) is a cellular model of Hebbian synaptic plasticity which is believed to underlie memory formation. In an attempt to establish a STDP paradigm in CA1 of acute hippocampal slices from juvenile rats (P15–20), we found that changes in excitability resulting from different slice preparation protocols correlate with the success of STDP induction. Slice preparation with sucrose containing ACSF prolonged rise time, reduced frequency adaptation, and decreased latency of action potentials in CA1 pyramidal neurons compared to preparation in conventional ASCF, while other basal electrophysiological parameters remained unaffected. Whereas we observed prominent timing-dependent long-term potentiation (t-LTP) to 171 ± 10% of controls in conventional ACSF, STDP was absent in sucrose prepared slices. This sucrose-induced STDP deficit could not be rescued by stronger STDP paradigms, applying either more pre- and/or postsynaptic stimuli, or by a higher stimulation frequency. Importantly, slice preparation with sucrose containing ACSF did not eliminate theta-burst stimulation induced LTP in CA1 in field potential recordings in our rat hippocampal slices. Application of dopamine (for 10–20 min) to sucrose prepared slices completely rescued t-LTP and recovered action potential properties back to levels observed in ACSF prepared slices. Conversely, acute inhibition of D1 receptor signaling impaired t-LTP in ACSF prepared slices. No similar restoring effect for STDP as seen with dopamine was observed in response to the β-adrenergic agonist isoproterenol. ELISA measurements demonstrated a significant reduction of endogenous dopamine levels (to 61.9 ± 6.9% of ACSF values) in sucrose prepared slices. These results suggest that dopamine signaling is involved in regulating the efficiency to elicit STDP in CA1 pyramidal neurons.
synaptic plasticity; dopamine; isoproterenol; rat; hippocampal slice