Synaptic Transmission: Electrical, Chemical, and Neurotransmitters PDF

7.1 Synapses Synapse Intro -​ Location where a presynaptic axon meets a postsynaptic cell -​ Primarily presynaptic cell sending information to the postsynaptic cell -​ With some feedback from post- to presynaptic cell Synapse Locations -​ Synapses primarily form on the dendr...

7.1 Synapses Synapse Intro -​ Location where a presynaptic axon meets a postsynaptic cell -​ Primarily presynaptic cell sending information to the postsynaptic cell -​ With some feedback from post- to presynaptic cell Synapse Locations -​ Synapses primarily form on the dendrites of a neuron -​ Also formed with: -​ Cell body -​ Axon of other cells -​ Muscle cells -​ More! Synapses - Classes -​ Can be divided into two categories: -​ Electrical -​ Chemical Electrical Synapses -​ Very uncommon -​ Found in some reflex circuits -​ Pre- and postsynaptic cells are physically touching -​ Gap junctions from tunnels between cells that allow ions to freely flow between cells -​ Similar to leak channels -​ Extremely fast signaling  -​ Ions freely and quickly flow from one cell to the other with no gating mechanism -​ AP depolarization traveling down axon will directly carry over to next cell -​ The information passing between cells cannot be modulated -​ Unlike chemical synapses that are far more dynamic with their signaling Chemical Synapses -​ Almost all synapses in the nervous system -​ Pre- and postsynaptic separated by synaptic cleft -​ Microscopic gap between cells -​ Not physically touching -​ Neurotransmitters (NT) are released from the presynaptic cell -​ NTs then passively drift across the synaptic cleft -​ NTs bind to NT receptors on the postsynaptic cell membrane -​ NT receptors will perform some type of cellular function when the NTs bind -​ Change in membrane potential -​ Protein activation -​ Gene expression -​ Etc. -​ Far slower than electrical synapses -​ Needs to release NTs, let them drift, and activate receptor -​ Chemical synapses are far more dynamic in their signaling 7.2 Synaptic Transmission Synaptic Terminal Structure -​ The end of an axon -​ Aka axon bouton -​ Is the location where information is converted from an electrical signal (AP) to a chemical signal (NT) -​ Important structures for synaptic transmission include: -​ NT vesicles -​ SNARE complex proteins -​ Ca2+ voltage-gated channels -​ NT reuptake proteins NT Vesicles -​ Spheres made of the same material as the cellular membrane -​ Spheres are densely filled with NTs -​ Vesicles will only contain one type of NT -​ Each vesicles contains the same amount of NTs -​ Many NT vesicles are attached to the inside of the cellular membrane that is facing the synaptic cleft -​ Primed and ready to be quickly released into the cleft -​ Additional NT vesicles are not attached the membrane -​ Form a reserve pool which are ready to be attached to the membrane SNARE Complex -​ Vesicles are secured to the intracellular side of the membrane with SNARE complex proteins -​ Soluble N-ethylmaleimide-Sensitive Factor Attachment Proteins (SNAP) Receptors -​ Do not memorize full name -​ Responsible for: -​ Securing the vesicles to the membrane -​ Cause the NTs to be released into the synaptic cleft -​ SNARE complex is attached to the NT vesicles and membrane -​ Tightly secured the vesicle against the inside of the cellular membrane -​ Proteins are locked into a high stressed position -​ Containing potential energy used to release NTs -​ Like a clip held open, ready to clamp close -​ Proteins locked into high stress position by Ca2+ sensor proteins -​ When then Ca2+ sensors detect Ca2+ in the cell, it will release from the SNARE complex -​ Allowing those proteins to clamp close and expel their stored energy -​ SNARE complex clamping closed will apply force on the vesicle onto the cellular membrane -​ Will force the vesicle to fuse with the membrane -​ Recall: there are made of the same material, so the vesicle nicely melds into the membrane  -​ SNARE complex clamping closed will apply force on the vesicle onto the cellular membrane -​ Will force the vesicle to fuse with the membrane -​ Recall: they are made of the same material, so the vesicle nicely melds into the membrane -​ The vesicle is forced to fuse with the membrane by the SNARE complex -​ Cause its contents (NTs) to be released into the synaptic cleft Ca2+ Voltage-Gated Channels -​ Synaptic terminal also contains Ca2+ voltage-gated channel -​ Opens very quickly when the membrane potential reaches ~0mV -​ Has no inactivation mechanism NT Reuptake Proteins -​ Proteins embedded in the presynaptic cell membrane -​ Will bring NTs from the synaptic cleft back into the cell Synaptic Transmission Steps -​ Synaptic terminal with all the structures covered above -​ AP travels down from the axon into the synaptic terminal -​ Synaptic terminal greatly depolarizes, activating Ca2+ voltage-gated channels -​ Ca2+ rush into the synaptic terminal -​ SNARE complex Ca2+ sensors detect an increase of Ca2+ in the cell -​ SNARE complex force the NT vesicles to fuse with the membrane -​ Forcing NTs into the synaptic cleft  -​ NTs will drift across the synaptic cleft to bind to receptors on the postsynaptic cell -​ Causing some type of cellular function -​ NTs are cleared out of the synaptic cell and the postsynaptic cell stops responding Synaptic Cleft Clearance -​ Nervous system will clear out synaptic cleft of NTs quickly to prepare the synapse for the next wave of NTs -​ Three methods: -​ NT reuptake proteins -​ Degradation -​ Diffusion NT Reuptake -​ Proteins in the presynaptic cell bring NTs back into the cell -​ NTs can be either -​ Recycled to be reused -​ Broken down and components used for other processes Degradation -​ NTs are broken down by enzymes free floating in the synaptic cleft -​ Will clear out the NTs over time as they bind and break down the NTs Diffusion -​ NTs will float out of the synaptic cleft -​ Taken up by neighboring astrocytes Synaptic Cleft Clearance -​ Clearance processes will not significantly affect NT signaling in a healthy system -​ NTs are released in large quantities, so plenty of NTs will interact with a postsynaptic cell before NTs are cleared out 7.3 Receptors NT Receptors -​ NTs will drift across the synaptic cleft to bind to NT receptors -​ Receptors are proteins that are activated when a NT binds to their NT binding site -​ Receptors are ligand specific -​ Are activated by only one specific NT, other NTs will not activate the receptor -​ Other substances activate receptors by mimicking a given NT -​ NTs will resolutely bind and unbind with the receptors -​ Repeatedly turning function on and off -​ Will repeat until all NTs are cleared from synaptic cleft -​ Two classes of NT receptors: -​ Ionotropic -​ GPCR Ionotropic -​ More simple of the two classes -​ Ligand-gated ion channels -​ Channels and NT binding sites are a part of the same protein -​ NT binds to the receptor and will result in a change in membrane potential -​ EPSP -​ IPSP -​ Does not influence cellular functions in other ways GPCR -​ G protein-coupled receptor -​ Aka metabotropic receptors -​ More complex of the two receptor classes -​ Still have a NT binding site, but no ion channel built into the same protein -​ When NTs bind to GPCRs, the G proteins will detach from the internal side of the receptor protein -​ G proteins will activate other proteins to influence cellular processes -​ G proteins can facilitate a wide range of cellular processes -​ Open ion channels, changing membrane -​ Influence other proteins -​ Influence gene expression Ionotropic and GPCR Compared -​ GPCRs can also influence membrane potential, but does not directly contain the ion channel like ionotropic receptors do -​ Will activate separate ion channels with the G protein -​ Activating GPCR receptors are slower than ionotropic receptors -​ GPCRs typically result in long term influence of neural activity Receptors -​ The same NT can bind to a wide range of different receptors -​ Each receptor type can have a wide range of effects on the cell -​ The same NT can have inverse effects on cells based on the type of receptors that the postsnaptic cells have DA in the Basal Ganglia -​ The basal ganglia contains two pathways (network for neurons that do a specific process) -​ Direct Pathway: allows motor movements to happen -​ Indirect Pathway: prevents a motor movement from happening -​ Each basal ganglia pathway contains different classes of dopamine (DA) receptors with inverse effects -​ Direct Pathway: D1-excitatory -​ Indirect Pathway: D2-inhibitory -​ When DA is released in the basal ganglia, it will interact with both D1 and D2 receptors causing: -​ Direct Pathway: Excited -​ Indirect Pathway: Inhibited  -​ Causing the body to perform a motor movement -​ DA caused two opposite effects in the same brain area because of the receptor types found in networks of that brain area -​ Cell’s responses are dependent on the receptor type, not the NT type 7.4 Excitatory and Inhibitory NT Neuron Classification -​ Many neurons can be classified as either: -​ Excitatory -​ Inhibitory -​ Characterized by the effect on the postsynaptic cell Excitatory Neurons -​ Neurons which cause the postsynaptic cells to depolarize -​ Increasing AP likelihood -​ Typically forms synapses with the dendrites of the postsynaptic cell -​ Most excitatory neurons release glutamate (Glu) -​ The most common NT in the brain -​ Classified as an excitatory NT -​ Almost always excitatory -​ Seldomly acts as inhibitory signal in some cells -​ NTs are not intrinsically excitatory or inhibitory -​ Glu typically binds to glutamatergic receptors  -​ Ex. AMPA Receptors -​ Ionotropic Na+ receptor -​ Glu binds, allowing Na+ to rush into the cell -​ Depolarizing the membrane Inhibitory Neurons -​ Neurons which cause the postsynaptic cells to hyperpolarize -​ Decrease AP likelihood -​ Typically forms synapses with the cell body of the postsynaptic cell -​ Most inhibitory neurons release gamma-aminobutyric acid (GABA) -​ Second most common NT in the brain -​ Classified as an inhibitory NT -​ Almost always inhibitory -​ Excitatory in some niche cases -​ GABA typically binds to GABAergic receptors -​ Ex. GABAa Receptors -​ Ionotropic Cl- receptor -​ GABA binds, allowing Cl- to rush into the cell -​ Hyperpolarizing the membrane Excitatory & Inhibitory Neurons -​ Cells that produce Glu and GABA are produced across the whole brain -​ No centralized location -​ Both primarily interact with ionotropic receptors to either excite or inhibit other neurons 7.5 Neuromodulator NT Neuromodulator NT -​ Class of NTs are important for wide range of neural processes -​ Have more widespread influence of neural activity than the local signaling of Glu and GABA -​ 4 Majors NTs: -​ Acetylcholine (ACh) -​ Dopamine (DA) -​ Norepinephrine (NE) -​ Serotonin (5-HT) -​ Each NT interacts with a wide class of receptors that influence many neural processes -​ Not consistently excitatory or inhibitory -​ These differ from Glu and Gaba based on how they modulate the brain and how they are produced Modulation -​ Modulate the activity of other neurons -​ Primarily interact with GPCR, resulting in longer term cellular processes -​ When compared to Glu and GABA Production -​ Less prevalent than Glu and GABA -​ Each neuromodulator NT is produced in a centralized location where the cell body is located -​ Axons extend far distances to communicate with certain structures Production - DA Example -​ DA is produced in the midbrain -​ Axons extend to multiple targets -​ Basal Ganglia -​ Pituitary -​ Cortex -​ NTs are transported along axons to reach synaptic terminals and released in those locations Investigation -​ Neuromodulator NTs are being thoroughly investigated for their role in -​ Cognition -​ Motor control -​ Neurological disorder -​ Clinical Depression -​ Substance Abuse Disorder -​ Generalized Anxiety -​ Etc. Popular Culture -​ Over generalizations about neuromodulator NTs are very common -​ Be mindful of social media, podcasts, and videos making big claims that seem to straightforward -​ Always check sources