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Dopaminergic Synapse | GABAergic Synapse | Glutamatergic Synapse | Synaptic Vesicle
Dopaminergic Synapse
Alterations in Dopamine (DA) neurotransmission are thought to play critical roles in Parkinson’s Disease, schizophrenia, as well as drug abuse and alcoholism. Tyrosine Hydroxylase (TH) is the rate limiting enzyme that controls the level of DA in the cell. Antibodies to TH are some of the most widely used neuronal biomarkers as TH signals the presence of dopamine. TH is highly regulated by a number of protein kinases.
At the receptor level DA interacts with D2 receptors on both the presynaptic and post-synaptic membrane. Activation of the D2 receptors often inhibits the production of cAMP while DA interaction with the D1 type of DA receptors leads to an increase in cAMP. These changes in cAMP levels lead to a complex set of signals involving downstream targets of cAMP-dependent protein kinase, which in turn lead to the complex intracellular effects of DA signaling.
At the receptor level DA interacts with D2 receptors on both the presynaptic and post-synaptic membrane. Activation of the D2 receptors often inhibits the production of cAMP while DA interaction with the D1 type of DA receptors leads to an increase in cAMP. These changes in cAMP levels lead to a complex set of signals involving downstream targets of cAMP-dependent protein kinase, which in turn lead to the complex intracellular effects of DA signaling.
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GABAergic Synapse
Gamma-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. Alterations in GABA inhibition have been implicated in epilepsy, as well as anxiety, Alzheimer’s disease, dementia, schizophrenia, and alcoholism. There are two principal classes of GABA receptors: GABA-A and GABA-B receptors. GABA A receptors are coupled to an ion channel that is permeable to Cl- and are primarily responsible for the inhibitory effect of GABA. The GABA A receptor has multiple subunits α, β, and γ; each of which have multiple isoforms. The various GABA A subunits can be regulated by phosphorylation via serine/threonine kinases and tyrosine kinases which can affect membrane localization and/or function of the receptors. GABA B receptors are g-protein coupled receptors that are linked to potassium channels. As with the GABA A receptors the GABA B receptors can be regulated by phosphorylation.
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Glutamatergic Synapse
Glutamate is the neurotransmitter principally responsible for excitatory synaptic transmission in the central nervous system. Glutamate receptors can be divided into two groups (ionotropic or metabotropic) according to the mechanism by which their activation gives rise to a postsynaptic current. The two ionotropic subtypes of glutamate receptors can be activated selectively by either AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) or NMDA (N-Methyl-D-aspartic acid). AMPA receptors mediate most excitatory glutamatergic transmission and contain three different subunits: GluR1-GluR3. NMDA receptors also have multiple subunits NMDAR1 and NMDAR2A- NMDAR2D. There are also multiple splice variants of the NR1 subunit, which is part of the heterotetramer that makes up the NMDA receptor. Both the AMPA and the NMDA receptors are regulated by phosphorylation, which in turn influences either the membrane localization or channel function.
The metabotropic subunit of glutamate receptors is called the metabotropic glutamate receptor (mGluR). mGluRs are g-protein coupled receptors and they also have multiple subunits: mGluR1-mGluR8. Glutamatergic function plays key roles in many diseases including dementia, Alzheimer’s disease, epilepsy, stroke as well as a number of other neurological conditions.
The metabotropic subunit of glutamate receptors is called the metabotropic glutamate receptor (mGluR). mGluRs are g-protein coupled receptors and they also have multiple subunits: mGluR1-mGluR8. Glutamatergic function plays key roles in many diseases including dementia, Alzheimer’s disease, epilepsy, stroke as well as a number of other neurological conditions.
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Synaptic Vesicles
Synaptic vesicles are membranous structures that contain neurotransmitters and fuse with the presynaptic membrane during exocytosis of the neurotransmitters. There are a large number of synaptic vesicle associated proteins that are thought to influence numerous vesicle functions (e.g. membrane association and fusion, vesicle recycling and neurotransmitter transport). Most prominent among these are synapsin and synaptophysin, which are both extremely widely used as neuronal markers for synaptic vesicles. Virtually all of these synaptic vesicle proteins are modulated by protein phosphorylation.
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