4- Neurophysiology- Pt 3.docx

- **Neurophysiology: General Info** - **Neurons** are the core components of the brain, spinal cord, and nerves. - **Dendrites** integrate incoming information and decide if an action potential will be produced by the neuron. - Dendritic spines are small me...

- **Neurophysiology: General Info** - **Neurons** are the core components of the brain, spinal cord, and nerves. - **Dendrites** integrate incoming information and decide if an action potential will be produced by the neuron. - Dendritic spines are small membranous protrusions that cover dendrites which are only present on some neurons. - Each dendritic spine can synapse with different axons, allowing the dendrite to have the capability of communicating with up to hundreds of axons. - Dendritic patterns of the neuron can change and may increase or decrease. - Growing dendrites are associated with a stimulates or enriched environment. - **Axons** can range from being a few micrometers long to being 10meters long, depending on the species and location it is in. - Axons contain the majority of the cellular cytoplasm which plays a role in the axon's length. - Axons can also contain the following organelles: mitochondria, lysosomes, neurofibrils, neurotubules, small vesicles, and enzymes. - Axonal proteins are synthesized by the soma (cell body) and transported to the axon. - The cytoskeleton and other proteins work by transporting different cargos into both directions. - Axonal protein examples include: organelles containing mitochondria and vesicles containing neurotransmitters. - **En Passante synapses** (interfaces) are used as the electrical signal passes by to the axon terminal. - The **Axosecretory** synapse interface is where the axon terminal secretes directly into the bloodstream. - **Axoplasmic Transport** - **Anterograde transport** - Anterograde transport is related to synaptic components. - An example of anterograde transport would be the flow of synaptic vesicles and mitochondria. - **Retrograde transport** - Retrograde transport is related to cargo for degradation. - An example of retrograde transport would be recycled membrane vesicles. - **Functional Types of Synapses** - **Chemical synapse** - Chemical synapses participates in unidirectional transmission. - Chemical synapses are the most common form of a synapse. - In chemical synapses, the presynaptic neuron will secrete neurotransmitters, which will act on receptor proteins in the postsynaptic neuron. - Chemical synapses can be inhibitory or excitatory. - **Electrical synapse** - Electrical synapses allow for bidirectional transmission. - Electrical synapses co-exist and interact with chemical synapses by promoting synchronous firing of a group of interconnected neurons. - **Gap junctions** allow for the free movement of ions from the interior of once cell to the interior of the cell next to it. - Gap junctions are clusters of ion channels that connect the cytoplasm of adjacent cells together. - **Neurotransmitter: Types** - Neurotransmitters can be conventional or unconventional. - **Conventional** - Conventional neurotransmitters act by binding to the receptors on the post-synaptic cell. - Conventional neurotransmitters are stored in vesicles. - An action potential will take place, causing calcium to enter the axon terminal, which will in turn, cause the release of conventional neurotransmitters. - **Small (organic) molecule conventional neurotransmitters include:** - Amino acids: Glutamate; GABA (gamma-aminobutyric acid), glycine - Amines: Acetylcholine, epinephrine, norepinephrine, dopamine, serotonin, and histamine - Purines: ATP, adenosine - **Large molecule** (which are composed of 3 or more amino acids) **conventional neurotransmitters include:** - Endorphins and encephalins which inhibit pain - Substance P which carries out pain signals - Neuropeptide Y which increases food intake and storage of energy as fat - **Unconventional** - Unconventional neurotransmitters are not stored in vesicles and are capable of sending signals backwards (from postsynaptic to presynaptic). - Unconventional neurotransmitters do not require receptors, allowing them to cross the cell membrane and act on molecules directly inside of the cell. - **Endocannabinoid** (unconventional neurotransmitters) - Endocannabinoid unconventional neurotransmitters are lipid-based neurotransmitters that bind to cannabinoid receptors (CB1 and CB2). - AEA (Anandamide) and 2-AG (2-arachinoyl-glycerol) are examples of endocannabinoids that are synthesized by the body. - THC and CBD are examples of endocannabinoids that are found in plants. - The endocannabinoid system is involved in the following physiological processes: appetite, pain sensation, mood, memory, and pharmaceutical effects of Cannabis sativa. - **Gasotransmitter** (unconventional neurotransmitters) - Gasotransmitter unconventional neurotransmitters are small molecules of gas (such as NO, CO, and hydrogen sulfide) that are freely permeable to the membrane. - An examples of Gasotransmitters would be Blood vessels signaling to smooth muscle, causing NO (nitric oxide) to be produced by some neurons, as it is required for normal performance of eye movement. - **Neurotransmitter: Examples** - Adrenaline stimulates the fight or flight response. - GABA stimulates a calming response. - Acetylcholine stimulates learning. - Glutamate stimulates memory. - Endorphins stimulate the feeling of euphoria. - Serotonin impacts overall mood by helping with sleep cycles and contributing to a feeling of happiness. - Dopamine stimulates the feeling of pleasure. - Noradrenaline stimulated concentration. - **Neurotransmitter: Actions** - The action of a neurotransmitter in the postsynaptic membrane depends on receptor proteins. - **Ionotropic receptors** - Ionotropic receptors are neurotransmitter receptors that directly gate ion (cation or anion) channels. - **Cation channels** are opened by excitatory neurotransmitters and induce depolarization. - Sodium channels are an example of a cation channel. - **Anion channels** open by inhibitory neurotransmitter and induce hyperpolarization. - Chloride channels are an example of an anion channel. - **Metabotropic receptors** - Metabotropic receptors are neurotransmitter receptors that act through second messenger systems. - **GPCR (G protein coupled receptors)** are examples of metabotropic receptors. - GPCR's open specific ion channels through the postsynaptic membrane. - GPCR's activate: - Gene transcription - The CAMP pathway - One or more intracellular enzymes. - **Action Potential: General Info** - **Resting potential** - The resting potential of a typical neuron is between -60 to -70millivolts, where the interior of the cell is more negative than the exterior. - **Graded potentials** are brief local changes in the post synaptic membrane. - Graded potentials modulate the postsynaptic membrane by shifting the resting membrane potential. - If the graded potential is shifted [towards] the threshold potential, depolarization will occur. - If the graded potential is shifted [away from] the threshold potential, hyperpolarization will occur. - The **Trigger zone** is more sensitive to depolarizing actions of the local currents. - All action potentials generated at the trigger zone are identical and propagate down the axon without losing strength, due to the domino effect taking place allowing the action potential to travel long distances. - The speed of an action potential's conduction depends on the axon diameter and degree of myelination of the axon. - In small, unmyelinated axons, an action potential can be conducted as low as 0.25m/sec. - In large, myelinated axons, an action potential can be conducted as high as 10m/sec. - **Saltatory conduction** involves action potentials jumping from node to node (on the nodes of Ranvier). - Action potentials only occur at the nodes of Ranvier in myelinated fibers, as the action potential gets regenerated at the nodes. - The **Nodes of Ranvier** are rich in ion channels. - During an action potential, sodium influx depolarizes the membrane. - The electrical (passive and decremental sodium) current of the action potential flows through the axoplasm inside of the axon. - **Depolarization** shifts the membrane potential to be more positive in charge. - Depolarization typically involves excitatory neurotransmitter opening cation channels. - An example would be: Glutamate binding to specialized receptor to allow for the transport od calcium, potassium, or sodium. - **EPSP (Excitatory postsynaptic potentials)** are involved in depolarizing graded potentials, driving the membrane potential towards threshold. - ESPS synapses are called "excitatory synapses". - **Hyperpolarization** shifts the membrane potential to be more negative in charge. - Hyperpolarization typically involved inhibitory neurotransmitters opening anion channels. - An example would be: GABA binding to a ligand-gated chloride channel. - **IPSP (Inhibitory postsynaptic potentials)** are involved in hyperpolarizing graded potentials. - IPSP synapses are called "inhibitory synapses". - The **Threshold potential** is defined as being the minimum voltage required to trigger an action potential. - The threshold potential typically occurs at -55millivolts. - **Action potentials are generated by:** - Step 1: In response to neurotransmitters from presynaptic neurons, neurons are receiving hundreds of inputs from other neurons. - Step 2: This triggers the generation of graded potentials. - The amplitude of the graded potential is directly proportional to the intensity of the stimulus applied at the synaptic site. - Each synaptic site generates graded potentials. - Step 3: Thousands of graded potentials occur at cell bodies and dendrites and they travel to reach the axon hillock (AKA: trigger zone). - Step 4: Once in the trigger zone, the graded potentials are integrated to generate action potentials. - This action potential will only occur if the sum of the graded potentials exceeds the threshold potential. - If this requirement is not met, an action potential will not occur and the graded potential will decay. - Step 5: If the action potential is generated, then the action potential will propagate along the axon. - **Graded Potential: Summation** - Numerous presynaptic axons converge on a postsynaptic neuron, generating thousands of IPSPs and EPSPs. - The axon hillock is able to process all graded potentials by algebraic processing of adding or subtracting potential charges. - The axon hillock continues to process graded potentials as along as: - The sum of all graded potentials are under the threshold potential. - The presynaptic changes occur faster than the decay rate of the graded potential in the postsynaptic neuron. - Graded potentials can be involved in either spatial summation or temporal summation. - **Spatial summation** - In spatial summation, graded potentials are induced by [different (more than one)] synapses summated in the postsynaptic neuron. - Simultaneous summation of IPSP and EPSP graded potential also occur during spatial summation. - **Temporal summation** - In temporal summation, successive discharges from [a single] presynaptic terminal summates in the postsynaptic neuron, if they are rapid enough. - Temporal summation occurs when 2 graded potentials from 1 presynaptic neuron occur close together in time. - **Action Potential Conduction: Steps** - Step 1: In response to a signal, the soma end of the axon becomes depolarized. - Step 2: Depolarization spreads down the axon. Meanwhile, the first part of the membrane repolarizes. - Because the sodium channels are inactivated and additional potassium channels are opened, the membrane cannot depolarize again. - Step 3: The action potential continues to travel down the axon. - **Saltatory Conduction: Steps** - Step 1: As charges spread down an axon, myelination prevents ions from leaking out across the plasma membrane. - Step 2: Charge spreads unimpeded until it reaches an unmyelinated section of the axon, called the Nodes of Ranvier, which is packed with sodium channels. - Step 3: In this way, electrical signals continue to jump down the axon much faster than they can move down an unmyelinated cell.