Lecture 7 Notes
Lecture 7 Notes Biol-K416
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This 4 page Class Notes was uploaded by Malissa Notetaker on Saturday October 1, 2016. The Class Notes belongs to Biol-K416 at Indiana University Purdue University - Indianapolis taught by Dr. Jason Meyer in Fall 2016. Since its upload, it has received 4 views. For similar materials see Cell & Molecular Neuroscience in Neuroscience at Indiana University Purdue University - Indianapolis.
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Date Created: 10/01/16
Cellular and Molecular Neuroscience Lecture 6 9/21/16 Topic: Neurotransmitters and Their Receptors ● Categories of NTs: ○ Although there are > 100 different NTs, they can be classified into two main groups: ■ Neuropeptides relatively large NTs composed of 3 36 amino acids ● Synthesized in cell bodies ■ Smallmolecule NTs typically individual amino acids or small molecules. Many common NTs fall into this category ● Synthesized in axon terminals ● Excitatory NTs: ○ Acetylcholine ○ Glutamate ○ Dopamine ○ Epinephrine ○ Norepinephrine ○ Histamine ○ Serotonin ○ When excitatory NT binds, what flows in? ■ Na+ (most likely), Ca2+, could be K+ but not likely ○ If no reuptake: ■ Can start addiction ■ Can weardown postsynaptic neuron ● Acetylcholine ○ Synthesized in axon terminals from acetyl CoA and Choline ○ Synthesis catalyzed by Choline Acetyltransferase (ChT) ○ Choline taken up from the environment through choline transporter (ChT) ○ Loaded into vesicles by vesicular ACh transporter (VAChT) loads 10,000 molecules in each vesicle ○ Degraded in synapse by Acetylcholinesterase ○ Most commonly associated with neuromuscular junction bc connects NS w/ muscles to allow motor activity ● Structure of the nACh receptor ○ Known as “nicotinic” receptor due to the ability of nicotine to bind to it ○ Nonselective cation channel (only allows + charges) that generates EPSPs and EPPs (endplate potentials) ○ Constriction in pore serves as the “gate” that is opened by conformational change of protein when ACh is bound ○ What would you call a NT receptor that opens as a channel in response to NT binding? ■ Answer: ionotropic receptors or ligandgated ion channels ● Glutamate as an Excitatory Neurotransmitter ○ Glutamate is the most common NT in the CNS ○ Nearly all excitatory neurons in the CNS are glutamatergic ○ Over ½ of all brain synapses use glutamate ○ Packaged into vesicles by vesicular glutamate transporters (VGLUTs) ○ Typically removed by one of the excitatory amino acid transporters (EAATs), found either on presynaptic terminal or on surrounding astrocytes ○ Returned to terminal from glial cells through SN1 protein on glial cells and SAT2 protein on terminals ● Types of Glutamate Receptors ○ 3 main types of receptors (names after agonists that activate them: ■ AMPA ■ NMDA ■ Kainate ○ All are glutamategated cation channels that allow flow of Na+ and K+ (sometimes Ca+) ● Actions of Glutamate Receptors ○ EPSCs (excitatory postsynaptic currents) produced by AMPA receptors typically larger that other glutamate synapses ○ EPSCs produced by NMDA receptors are typically slower than other glutamate synapses ○ Kainate receptors are weakest ● Properties of the NMDA receptor ○ Pore of NMDA channel allows flow of Ca2+ in addition to Na+ and K+ ■ Pores are larger ○ Mg2+ blocks NMDA channel at hyperpolarized membrane potentials, serving as a “gate” ○ These features are thought to underlie certain features such as synaptic plasticity ● Inhibitory Neurotransmitters GABA and Glycine ○ GABA is the most common inhibitory NT ■ Is packaged into vesicles due to vesicular inhibitory amino acid transporter (VIAAT) ● Removal of GABA from synapse ○ Similar to glutamate due to transporter proteins on terminals and astrocytes ○ Removed by GABA transporters known as GATs ○ Uptaken GABA is converted to succinate ○ Other methods of degradation of GABA include formation of other chemicals ● Structure and Function of GABA receptors ○ Three types of receptors: ■ GABA A ■ GABA B ■ GABA C ○ Ion channels gated by presence of GABA ○ Cl ions are the main permeant ion ○ Benzodiazepines bind and are used to treat epilepsy ■ Modulate activity of GABA receptors ○ Barbiturates bind such as pentobarbital and are used for anesthesia ■ sleepy/relaxed ● Glycine as an inhibitory neurotransmitter ○ Use of glycine more restricted in nervous system than other NTs ○ Synthesized from serine through use of serine hydroxymethyltransferase ○ Transported to vesicles through vesicular inhibitory amino acid transporter (VIAAT) ■ Same as GABA ○ Glycine is removed from the synapse by glycine transporters on axon terminals and astrocytes ○ Postsynaptic receptors are chloride channels similar to GABA receptors ● Biogenic Amines ○ Regulate many brain functions, in particular those associated with behavior ○ Consist of 5 different NTs: ■ Catecholamines dopamine, norepinephrine, and epinephrine ■ Others histamine and serotonin ● Synthesis of Catecholamines ○ All three are derived from tyrosine ○ Tyrosine converted to DOPA through use of tyrosine hydroxylase ○ DOPA converted to Dopamine through use DOPA decarboxylase ○ Dopamine converted to norepinephrine through use of dopaminebeta hydroxylase ○ Norepinephrine converted to epinephrine through use of Phenylethanolamine Nmethyltransferase ● Dopamine in the brain ○ Major dopaminecontaining region is the corpus striatum ■ Receives input from substantia nigra and coordinates body movements ○ At synapse, dopamine is loaded into vesicles due to vesicular monoamine transporters (VMATs) ○ Cleared from synapse due to dopamine transporters (DATs) on terminals and on astrocytes ○ Degraded by monoamine oxidase (MAO) and catechol O methyltransferase (COMT) found in neurons and glia ■ MAOIs prevent degradation of dopamine ● Serotonin in the brain ○ Aka 5hydroxytryptamine (5HT) ○ Found primarily in raphe nucleus and pons of brainstem with widespread projections to the forebrain ○ Cleared from synapse through specific serotonin transporter (SERT) ○ Numerous serotonin receptors identified, implicated in behaviors such as emotions, circadian rhythms, mental arousal