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Physio Psyc Ch.3
Sherrington • Sherrington deduced the properties of the synapse from his experiments on reflexes (an automatic muscular response to stimuli). • Reflex arc: the circuit from sensory neuron to muscle response.
Reflex Arcs • Reflexes are slower than conduction along an axon • Several weak stimuli presented at slightly different times or location produce a stronger reflex than a single stimuli does. • Excitation of one set of muscles leads to a relaxation of others.
Temporal summation • Repeated stimuli within a brief time having a cumulative effect.
Temporal summation • Presynaptic neuron (the neuron that delivers the synaptic transmission) • Postsynaptic neuron (the neuron that receives the message). • Graded potentials: Either depolarization (excitatory) or hyperpolarization (inhibitory) of the postsynaptic neuron.
EPSP • A graded depolarization is known as an excitatory postsynaptic potential (EPSP) and occurs when Na+ ions enter the postsynaptic neuron. EPSPs are not action potentials: The EPSP’s magnitude decreases as it moves along the membrane.
Spatial summation • Several synaptic inputs originating from separate locations exerting a cumulative effect on a postsynaptic neuron.
Inhibitory postsynaptic potential • (IPSP): A temporary hyperpolarization of a postsynaptic cell (this occurs when K+ leaves the cell or Cl- enters the cell after it is stimulated).
EPSP, IPSP & APs • The probability of an action potential on a given neuron depends on the ration of EPSPs to IPSPS at a given moment. • Spontaneous firing rate: The ability to produce action potentials without synaptic input (EPSPs and IPSPs increase or decrease the likelihood of firing action potentials).
Chemical Events at the Synapse • In most cases, synaptic transmission depends on chemical rather than electrical stimulation. This was demonstrated by Otto Loewi’s experiments where fluid from a stimulated frog heart was transferred to another heart. The fluid caused the new heart to react as if stimulated.
Major events at a synapse • Neurons synthesize chemicals called neurotransmitters. • Neurons transport the neurotransmitters to the axon terminal. • Action potentials travel down the axon. At the axon or presynaptic terminal, the action potentials cause calcium to enter the cell which leads to the release of neurotransmitters from the terminal into the synaptic cleft (space between the presynaptic and postsynaptic neuron).
Major events at a synapse • Neurotransmitters, once released into the synaptic cleft, attach to receptors and alter activity of the postsynaptic neuron. • The neurotransmitters will separate from their receptors and (in some cases) are converted into inactive chemicals. • In some cells, much of the released neurotransmitter is taken back into the presynaptic neuron for recycling. In some cells, empty vesicles are returned to the cell body.
Major events at a synapse • Although not conclusively proven, it is likely that some postsynaptic cells send negative feedback messages to slow further release of transmitter by the presynaptic cells
Neurotransmitters • Chemicals released by one neuron at the synapse and affect another neuron are neurotransmitters.
Neurotransmitters • Amino acids: Acids containing an amine group (NH2). • Peptides: Chains of amino acids. A long chain is called a polypeptide; a still longer chain is a protein. • Acetylcholine: A chemical similar to an amino acid, with the NH2 group replaced by an N(CH3)3 group.
Neurotransmitters • Monoamines: Neurotransmitters containing an amine group (NH2) formed by a metabolic change of an amino acid. • Purines: Adenosine and several of its derivatives. • Gases: Includes nitric oxide (NO) and possibly others.
Synthesis of neurotransmitters • Catecholamines (Dopamine, Epinephrine, and Norepinephrine: Three closely related compounds containing a catechol and an amine group. • Choline is the precusor for acetylcholine. Choline is obtained from certain foods or made by the body from lecithin. • The amino acids phenylalanine and tyrosine are precursors for the catecholamines. • The amino acid tryptophan is the precursor for serotonin. The amount of tryptophan in the diet controls the levels of serotonin.
Transport of Neurotransmitters • Certain neurotransmitters, such as acetylcholine, are synthesized in the presynaptic terminal. However, larger neurotransmitters, like peptides, are synthesized in the cell body and transported down the axon to the terminal. • Transporting neurotransmitters from the cell body to the axon terminal can take hours or days in long axons.
Release and Diffusion of Transmitters • Neurotransmitters are stored in vesicles (tiny nearly spherical packets) in the presynaptic terminal. (Nitric oxide is an exception to this rule, as neurons do not store nitric oxide for future use). There are also substantial amounts of neurotransmitter outside the vesicles.
Release and Diffusion of Transmitters • When an action potential reaches the axon terminal, the depolarization causes voltage-dependent calcium gates to open. As calcium flows into the terminal, the neuron releases neurotransmitter into the synaptic cleft for 1-2 milliseconds. This process of neurotransmitter release is called exocytosis.
Release and Diffusion of Transmitters • After being released by the presynaptic neuron, the neurotransmitter diffuses across the synaptic cleft to the postsynaptic membrane where it will attach to receptors. • The brain uses dozens of neurotransmitters, but no single neuron releases them all.
Release and Diffusion of Transmitters • Each neuron releases the same combination of neurotransmitters at all branches of its axon. • A neuron may receive and respond to many neurotransmitters at different synapses.
Postsynaptic Cell • A neurotransmitter can have two types of effects when it attaches to the active site of the receptor: ionotropic or metabotropic effects.
Postsynaptic Cell • Ionotropic effects: Neurotransmitter attaches to the receptor causing the immediate opening of an ion gate (e.g., glutamate opens Na+ gates).
Postsynaptic Cell • Metabotropic effects: Neurotransmitter attaches to a receptor and initiates a cascade of metabolic reactions. This process is slower and longer lasting than ionotropic effects. Specifically, when the neurotransmitter attaches to the receptor it alters the configuration of the rest of the receptor protein; enabling a portion of the protein inside the neuron to react with other molecules.
Metabotropic effects • Activation of the receptor by the neurotransmitter leads to activation of G-proteins which are attached to the receptor.
Metabotropic effects • G-proteins: A protein coupled to the energy-storing molecule, guanosine triphosphate (GTP). • Second messenger: Chemicals that carry a message to different areas within a postsynaptic cell; the activation of a G-protein inside a cell increases the amount of the second messenger.
Neuromodulators • Neurotransmitters, mainly the peptide neurotransmitters, that do not by themselves strongly excite or inhibit a neuron, instead they alter (modulate) the effects of a neurotransmitter.
Hormones • A hormone is a chemical that is secreted primarily by glands but also by other cells and conveyed by blood to other organs whose activity it influences. • Unlike neurotransmitters which are released directly to another neuron, hormones convey messages to any organ that can receive it. • Endocrine glands produce hormones.
Hormones • Protein hormones and peptide hormones are composed of chains of amino acids. Protein and peptide hormones bind to membrane receptors and activate a second messenger within the cell—exactly the same process as at a metabotropic synapse. Some chemicals can act as both neurotransmitters and hormones such as epinephrine, norepinephrine, insulin and oxytocin.
Hormones • Hormones secreted by the brain control the secretion of other hormones. • The pituitary gland is attached to the hypothalamus and consists of two distinct glands, the anterior pituitary and the posterior pituitary.
Hormones • The posterior pituitary is composed of neural tissue like the hypothalamus. Two hormones, oxytocin and vasopressin (also known as antidiuretic hormone) are released from the posterior pituitary however both of these hormones are synthesized in the hypothalamus.
Hormones • The anterior pituitary is composed of glandular tissue and synthesizes and releases six hormones. The hypothalamus controls the release of these six hormones by secreting releasing hormones that stimulate or inhibit the release of the following hormones: adrenocorticotropic hormone, thyroid stimulating hormone, prolactin, somatotropin (also known as growth hormone), follicle-stimulating hormone, luteinizing hormone.
Inactivation and Reuptake of Neurotransmitters • Neurotransmitters become inactive shortly after binding to postsynaptic receptors. Neurotransmitters are inactivated in different ways. • Acetylcholinesterase (AChE): Found in acetylcholine (ACh) synapses; AChE quickly breaks down Ach after it releases from the postsynaptic receptor.
Inactivation and Reuptake of Neurotransmitters • After separation from postsynaptic receptor, serotonin and the catecholamines are taken up by the presynaptic neuron. This process is called reuptake; it occurs through specialized proteins called transporters. • Some serotonin and catecholamine molecules are converted into inactive chemicals by enzymes such as COMT (converts catecholamines) and MAO (converts both catecholamines and serotonin).
Negative Feedback From the Postsynaptic Cell • Autoreceptors: presynaptic receptors sensitive to the same neurotransmitter they release. Autoreceptors detect the amount of transmitter released and inhibit further synthesis and release after it reaches a certain level.
Negative Feedback From the Postsynaptic Cell • Postsynaptic neurons can respond to stimulation by releasing special chemicals that travel back to the presynaptic terminal where they inhibit further release of transmitter. Nitric oxide, anandamide, and 2-AG (sn-2 arachidoylglycerol) are three such chemicals.
Drugs and Synapses • Drugs can affect synapses by either blocking the effects (an antagonist) or mimicking (increasing) the effects (an agonist) of a neurotransmitter. A drug that is a mixed agonist-antagonist is an agonist for some behavioral effects or doses and an antagonist for others.
Drugs and Synapses • Drugs can influence synaptic activity in many ways, including altering synthesis of the neurotransmitter, disrupting the vesicles, increasing release, decreasing reuptake, blocking its breakdown into inactive chemicals, or directly simulating or blocking postsynaptic receptors.
Drugs and Synapes • Affinity: How strongly the drug attaches to the receptor. • Efficacy: The tendency of the drug to activate a receptor.
Drugs • Drugs are categorized by their predominant actions. For example, amphetamine and cocaine are stimulants, opiates are narcotics and LSD is a hallucinogen. Despite these differences, nearly all abused drugs directly or indirectly stimulate the release of dopamine in the nucleus accumbens (a small subcortical area rich in dopamine receptors).
Drugs • Stimulant drugs (e.g., amphetamines, cocaine, etc.) produce excitement, alertness, elevated mood, decreased fatigue, and sometimes motor activity. Each of these drugs increases activity at dopamine receptors, especially at D2, D3, and D4 receptors. Stimulant drugs are often highly addictive.
Stimulants • Amphetamine increases dopamine release from presynaptic terminals by reversing the direction of the dopamine transporter. • Cocaine blocks the reuptake of catecholamines and serotonin at the synapse. The behavioral effects of cocaine are believed to be mediated primarily by dopamine and secondarily by serotonin. • The effects of amphetamine and cocaine are both short-lived, because of the depletion of dopamine stores and tolerance.
Stimulants • Prolonged use of cocaine can cause long-term changes in brain metabolism and blood flow, increasing the risk of stroke, epilepsy, and memory impairments. • Methylphenidate (Ritalin): Stimulant currently prescribed for Attention Deficit Disorder (ADD); works like cocaine by blocking reuptake of dopamine at presynaptic terminals. The effects of methylphenidate are much longer lasting and less intense as compared to cocaine.
Stimulants • Methylenedioxymethamphetamine (MDMA or “ecstasy”) is a stimulant at low doses primarly increasing the levels of dopamine, however at higher doses it also releases serotonin and produces hallucinogenic effects. • MDMA destroys serotonin axons in laboratory animals. Deficits in serotonin synthesis and release have also been found in humans.
Nicotine • Compound found in tobacco. Stimulates the nicotinic receptor (a type of acetylcholine receptor) both in the central nervous system and neuromuscular junction of skeletal muscles; can also increase dopamine release by attaching to neurons that release dopamine in the nucleus accumbens. Repeated use of nicotine leads to decreased sensitivity in nucleus accumbens cells responsible for reinforcement.
Opiates • Derived from (or similar to those derived from) the opium poppy. Common opiates include morphine, heroin, and methadone. Opiates have a net effect of increasing the release of dopamine by stimulating endorphin receptors. Opiates also decrease activity in the locus coeruleus which results in decreased response to stress and decreased memory storage.
Marijuana • Contains the chemical Δ9-tetrahydrocannabionol (Δ9-THC) and other cannabinoids (chemicals related to Δ9-THC); Δ9-THC works by attaching to cannabinoid receptors. Anandamide and sn-2 arachidonylglycerol (2-AG) are brain chemicals that bind to cannabinoid receptors.
Marijuana • Marijuana can be used medically to relieve pain or nausea, combat glaucoma (eye disorder) and to increase appetite. Common psychological effects of marijuana include intensification of sensory experience and the illusion that time is passing very slowly. Prolonged marijuana use is associated with impaired memory performance.
Hallucinogenics • Drugs that distort perception. Many hallucinogenic drugs like lysergic acid diethylamide (LSD) resemble serotonin and bind to serotonin type 2A (5-HT2A) receptors.