| Annotated protein: | Beta-1 adrenergic receptor (Beta-1 adrenoreceptor) (Beta-1 adrenoceptor). Gene symbol: ADRB1. Taxonomy: Mus musculus (Mouse). Uniprot ID: P34971 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ ADRB1 |
| Ontology domain: | Biological Process |
| SynGO term: | G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential (GO:0099579) |
| Synapse type(s): | Schaffer collateral synapse (CA3->CA1) |
| Annotated paper: | Winder DG, et al. "ERK plays a regulatory role in induction of LTP by theta frequency stimulation and its modulation by beta-adrenergic receptors" Neuron. 1999 Nov;24(3):715-26 PMID:10595521 |
| Figure(s): | Fig.2, 3A |
| Annotation description: | Beta1-Adrenergic receptors (ARs) are G-Protein coupled receptors that bind epinephrine and norepinephrine. In CA3-CA1 Schaffer collateral synapses of the hippocampus, beta1-ARs are selectively involved in the generation of late-LTP in a PKA-dependant manner and via activation of ERK. To induce robust LTP, a protocol was chosen in which prolonged (3min) 5Hz stimulation is paired with beta-AR activation by application of 1 uM Iso (Fig. 2A). The induction of this form of LTP is dependent on beta1-AR activation since it is abolished in beta1-KO and beta1/beta2-DKO mice (Fig.2C), but not in beta2-KO mice (Fig. 2D). Basal synaptic transmission in beta1-KO mice is normal (Fig. 2E) indicating a selective effect during LTP generation. This form of LTP is further dependent on PKA since LTP is reduced in the presence of the PKA-inhibitor KT5720 (Fig. 3A) and depends on activation of ERK, since inhibition of ERK by the use of MEK inhibitors (e.g. U0126; Fig. 3B) also reduces LTP. MEK inhibitors did not change fEPSP slopes (Fig. 4D), indicating that beta-AR activation by Iso does not transiently enhance presynaptic synaptic transmission. In contrast, during the 5 Hz stimulation, postsynaptic CA1 neurons are known to generate AP firing patterns and application of Iso during the tetanus increases the number of postsynaptic spikes (Fig. 5A, B, E). These findings indicate that beta1-AR activation enhances LTP generation via postsynaptic signaling pathways that enhance neuronal excitability. 17/8/2017 Pim - The effect on "neuronal excitability" is translated into the term 'regulation of postsynaptic membrane potential'. |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) Antagonist / agonist |
| Evidence tracking, Experiment Assay: | Field recordings |
| Annotator(s): | Noa Lipstein (ORCID:0000-0002-0755-5899) Cordelia Imig (ORCID:0000-0001-7351-8706) Vincent O'connor (ORCID:0000-0003-3185-5709) Nils Brose (ORCID:0000-0003-0938-8534) |
| Lab: | Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany |
| Additional literature: | Intracellular recordings in combination with pharmacological experiments in hippocampal CA1 pyramidal cells indicate that activation of beta-receptors causes a depolarization of neurons thereby increasing excitability. @ PMID:2873241 Beta1 adrenergic receptors expressed in chinese hamster ovary cells bind adrenaline and noradrenaline (Table 2). @ PMID:1848818 |
| SynGO annotation ID: | 1096 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |