Neuro 355 Fundamentals of Behavioral Neurobiology Notes PDF

**Neuro 355** **Fundamentals of Behavioral Neurobiology** **The neuron:** Structure and function - A single gene mutation can wreak havoc in the brain - Mutation may occur during a translation or transcription error - Example: [fragile x syndrome](https://www.youtu...

**Neuro 355** **Fundamentals of Behavioral Neurobiology** **The neuron:** Structure and function - A single gene mutation can wreak havoc in the brain - Mutation may occur during a translation or transcription error - Example: [fragile x syndrome](https://www.youtube.com/watch?v=SfkRXT1eTO0&t=1s) ***The neuron and its parts*** **The prototypical neuron** - Camillo Golgi (1873) developed a staining method that made all parts of the neuron visible - Demonstrated that neurons have 2 distinguishable parts: the soma (cell body) and the neurites (branches coming out of the cell body/soma) - There are 2 kinds of neurites: axons and dendrites: - Dendrites: receive input signals from other cells - Acting as receiving antennas - Other cells form connections along the dendrites - Axon: sends output signals to other cells - Highly branched - Many target neurons - Branch structures are seen in other cells, what makes axons/dendrites unique is the way that they communicate is exclusive to the brain - A neuron has a membrane (the skin) and the 3D shape it takes is determined by cytoskeleton - ***Cytoskeleton**: provides structure to the cell*, ie scaffolding **The cell membrane:** the skin of the membrane A self-organizing phospholipid bilayer (part phosphate, part lipid molecules) - **Bilayer**: 2 layers of molecules (common to all cells, not just neurons) - The lipid tail is hydrophobic, and so the thin layer of phospholipids is "folded" to "hide" the lipids from the water - **Proteins in the Membrane:** Embedded into the membrane are different kinds of proteins - Neurotransmitter receptors, ion channels, ion pumps, and enzymes are inserted in the membrane **The soma** (cell body): Overview\ Typically \~20 μm in diameter, but ranges 4-100 μm. - The cell membrane has other small membrane-enclosed objects inside called organelles - Inside the membrane is a salty, potassium-rich fluid: the **cytosol** - Floating in the cytosol are the **organelles** (Golgi complex, mitochondria, etc.) - Everything inside the cell membrane, except the cell nucleus, is called the CYTOPLASM - cytosol + organelles **= cytoplasm** - In addition to the cytoplasm, the cell contains a **nucleus** (DNA) - ***The nucleus:** The structure in a cell that contains the chromosomes. The nucleus has a membrane around it, and is where RNA is made from the DNA in the chromosomes.* - ***Nuclear envelope:** nucleus membrane. The membrane is perforated by tiny pores* - Function: Separates the contents of the nucleus from the cytoplasm and provides the structural framework of the nucleus **The DNA and Chromosomes** The DNA in the nucleus is a double-stranded braid (double helix) [tightly packed](https://www.youtube.com/watch?v=9kQpYdCnU14) into chromosomes - Chromosomes are condensed packs of DNA strings. We have 46 chromosomes (23 pairs): - 22 pairs autosomal - ***Autosomal**: non sex chromosomes* - 1 pair sex chromosomes - Contain all the genetic info. Each cell in out body contains exactly the same DNA. The trick is which part of the DNA is used in each cell - The genetic code is a blueprint for making proteins - The DNA strings are made of nucleotides: Adenine, Guanine, Thymine, Cytosine - Chromosomes have two complementary strands of DNA - Weak bonds join complementary nucleotides - Adenine pairs with Thymine - Guanine pairs with Cytosine - Because DNA is harder to read when tightly wound up (imagine reading a book without opening it), the DNA is left loose in the nucleus for ease of expression - The only time DNA is packaged is during cell division - Why? Imagine moving 100+ pieces of loose paper vs 100+ papers stapled together, which one is more likely to get lost? +-----------------------------------+-----------------------------------+ |  | **Rough Endoplasmatic Reticulum | | | (ER) and ribosomes** | | | | | | - ***The rough endoplasmic | | | reticulum**: a cellular | | | organelle composed of many | | | folds of tissues and | | | channels. It provides surface | | | area for chemical reactions | | | to take place. It is rough | | | because its surface is | | | covered with ribosomes. These | | | ribosomes produce proteins* | | | | | | | | | | | | - A "maze" of membrane dotted | | | with ribosomes | | | | | | | | | | | | - ***Ribosomes**: where | | | proteins are manufactured | | | according to the genetic | | | code* | | | | | | | | | | | | - Not all ribosomes are | | | embedded into the rough ER | +-----------------------------------+-----------------------------------+ **Smooth ER and The Golgi Apparatus** +-----------------------------------+-----------------------------------+ | - **Smooth ER:** like curtains | - **Golgi Apparatus**: | | that separate areas in the | functions as a factory in | | cell | which proteins received from | | | the ER are further processed | | - Folding of proteins, | and sorted for transport to | | regulate internal | their eventual destinations: | | concentration of calcium | lysosomes, the plasma | | | membrane, or secretion | | | | | | - Modifying proteins | | | (folding, cutting) | | | | | | - Packaging proteins for | | | export | +-----------------------------------+-----------------------------------+ **Mitochondria**: the powerhouse of the cell 1 mitochondrion, 2+ mitochondria - Produces energy (ATP - the fuel of the cell) from pyruvic acid + O~2~ - ***ATP**: adenosine triphosphate (*A chemical energy) - ATP is then used in all energy demanding reaction in the cell. The release of the phosphate releases energy (as burning of fuel releases energy) - Shaped like a bean. Has an inner membrane that is folded to create a matrix. - Uses Pyruvic Acid (made from fat, sugar or protein) to add one phosphate to Adenosine DiPhosphate to create ATP - CO2 is a by-product **The Cytoskeleton:** Maintains the shape of the neuron (scaffolding) - Although we called them scaffolding, they are not static but probably in continuous movement. - Composed of: Microtubules, Neurofilaments, Microfilaments: +-----------------------+-----------------------+-----------------------+ | **Microtubules** | **Neurofilaments** | **Microfilaments** | +=======================+=======================+=======================+ | - Large and hollow | - Neurofilaments | | | - Strands are made | | - Built from actin | | of tubulin | - Very strong | | | | | - Dynamically | | - run | | adjust cell shape | | longitudinally | | | | down neurites. | | | +-----------------------+-----------------------+-----------------------+ **From gene expression to protein synthesis** - Golgi stain showed that neurons have at least 2 distinguishable parts: The soma (cell body) and the neurites - 2 kinds of neurites: Axons and dendrites +-----------------------------------+-----------------------------------+ | - **Gene expressio**n: reading | - **Protein synthesis**: making | | the DNA | the protein | +-----------------------------------+-----------------------------------+ - If all the cells in our body have the same DNA, how is it that they have different shapes and different functions? - Answer: proteins **The function of proteins** 1. Determine the **structure** of neurons - The cytoskeleton 2. Determine the **function** of neurons Chemical reactions *inside* neurons - generation of ATP in mitochondria - synthesis of neurotransmitters - Properties of the cell *membrane* - Neurotransmitter receptors on dendrites - ***Neurotransmitters**: The chemicals used in communication between neurons* - Channels in axons required for propagation of signal **Structure of Proteins** Different proteins are assembled from various combinations of 20 Amino Acids - Proteins are poly-peptides (i.e, a long chain of amino acids) - Each amino acid has: - A central carbon - An amino group - A carboxyl group - A variable residue (R group) - Different amino acids have different residues - Residues can by hydrophilic [or] hydrophobic→ and that determines the 3D structure of the protein - Proteins are formed by Joining Amino Acids - Peptide bonds link different amino acids - The carboxyl and amino groups join - The shape of the protein depends on the amino acids that get joined together - Many combinations of amino acids are possible - Many shapes are possible - The shape of the protein determines its function  - Proteins have 4 levels of structure: 1. **Primary**: the chain of amino acids (which acids and in what order) 2. **Secondary**: the chain coils into alpha helix configuration 3. **Tertiary**: the coil bends into a complex 3 dimensional form 4. **Quaternary:** Several polypeptide chains bond together and form a very large molecule. - Above, it is a channel (pore) in the cell membrane - Heat: destroys the 3-D formations +-----------------------------------+-----------------------------------+ | **Genes code for Proteins** |  | | | | | DNA specifies the order of amino | | | acids in a protein | | | | | | - 3 nucleotides (a "codon") | | | specify a single amino acid | | | | | | - A gene is the sequence of | | | codons (required for a | | | sequence of amino acids) that | | | make up a given protein | | | | | | - Genes that are activated, | | | determine which proteins will | | | be synthesized | | +-----------------------------------+-----------------------------------+ **From DNA to proteins:** (transcription and translation)\ **Protein Synthesis** The first step is [Transcription] (of DNA into mRNA) 1. Strands of DNA separate and complementary bases line up on the coding strand to form ***messenger RNA** (mRNA)* - **Adenine** pairs with Uracil (a bit different from DNA pairs) - **Thymine** pairs with **Adenine** - **Guanine** pairs with **Cytosine** - **Cytosine pairs with Guanine** mRNA leaves the nucleus 2. The second step is [Translation] (creation) - ***RNA processing**: Ribosomes read the mRNA to make the protein* - Proteins made by free ribosomes will stay in the cytosol (e.g.: enzymes). - Whereas proteins made by ribosomes in the rough ER will end up in organelles or the membrane. +-----------------------------------------------------------------------+ | **How exactly do amino acids find the right codon?** | | | | - **Transfer RNA (tRNA):** Transfer RNA is an adaptor molecule | | composed of RNA, typically 76 to 90 nucleotides in length, that | | serves as the physical link between the mRNA and the amino acid | | sequence of proteins. | +=======================================================================+ | | +-----------------------------------------------------------------------+ **The genetic code** - The amino acids that are "fetched" by each codon - Each amino acid is coded by a triplet of 3 bases (nucleotides). - The final protein is sometimes cut from a much larger protein - e.g. beta-endorphin, corticotropin\... - The FMR1 gene provides instructions for making a protein called FMRP. This protein is present in many tissues, including the brain, testes, and ovaries. In the brain, it may play a role in synaptic genesis **The Resting Membrane potential (RMP)** **Action potentials and neuronal communication** How do neurons communicate information? Neurons conduct information over a distance using electrical signals - **[Action potential](https://www.youtube.com/watch?v=hGDvvUNU-cw&ab_channel=BrainFacts.org)*:*** *Electrical signal runs down the axon and releases neurotransmitters once it reaches the axon terminals* - Travels down the axon like a wave - Similar to how the tension in an archer's bow, when pulled back, has the *potential* to thrust the arrow forward when releasing the string - The neuronal membrane has an electrical potential (voltage) - **Electrical potential:** *Difference in electrical charge.  The amount of work needed to move a unit charge from one location* - The resting membrane potential (RMP) -65 mV - When the neuron is at ''rest'' (meaning has no inputs), ions are NOT evenly distributed across the membrane - Sodium (Na) and chloride (Cl) is highly concentrated outside of the cell, whereas potassium (K) is highly concentrated inside of the cell **The membrane** Why/how is there a difference in concentration between inside and outside of the cell? - The membrane is semi-permeable, due to the phospholipid bilayer - Ie, Polar ''head'' containing phosphate- loving water, and nonpolar ''Tail'' containing hydrocarbon- the swimmer - **Polar vs non polar**: *When things are different at each end, we call them polar* - Allows for crossing of lipid soluble molecules - Small unchanged, water-soluble molecules can cross - But [charged ions *cannot*] cross the membrane - Ions= (charged water soluble molecule) - Due to non-polar lipid bilayers: - Charged atoms or molecules of any size cannot cross the cell membrane (via simple diffusion) as the charges are repelled by the hydrophobic tails in the interior of the phospholipid bilayer. - Water is polar & ions attract cloud of water molecules - The effective size of the ions becomes larger (spheres of hydration) - [Ions *can*] cross through channels**:** - Channels contain a selective pore (hole): selection due to charge, size - By selecting ions according to *charge:* - \+ positive charged regions: inside the pores repel potassium, but allows chloride to passthrough the pores - \- negative charged region: allows positive ions to pass through the pores - By selecting channels based on *size:* - Ions of the same charge have different diameters of hydration (allows for potassium to pass, but not chloride) - Channels can open and close (gates) +-----------------------------------+-----------------------------------+ | Charged ions (water soluble | Ions | | molecules) | | +===================================+===================================+ | Why can't charged ions cross the | Why can ions cross through | | membrane? | channels | | | | | - | - Channels contain a selective | | | pore (hole) | | | | | | - Channels can open and close | | | (gates) | +-----------------------------------+-----------------------------------+ - **Spheres of hydration***: The charged particles will form hydrogen bonds with a surrounding layer of water molecules. This is referred to as a sphere of hydration and serves to keep the particles separated or dispersed in the water* **The resting membrane potential** Neurons conduct information over a distance using electrical signals Through communication in a complex chain between sensory neuron axons and motor neuron axons **Action potentials and neuronal communication** Neuronal communication is achieved via a chemical signal, the neurotransmitter, released at the axon terminals upon the arrival of an electrical signal travelling down the axon: the axon potential Neuronal communication: Electrical signals communication line: Sensory neuron → interneuron → motor neuron → motor output Why does the action potential exist? Because electrical charge in the cytosol of the axon is carried by electrically charged atoms (ions) inside of free electrons. This makes cytosol far less conductive than copper wire The axon is not well insulated and is bathed in intracellular fluid, which conducts electricity. Like water flowing down a leaky hose, electrical current passively conducting down the axon would not go very far before it would leak out To counter this, the axonal membrane has properties that enable it to conduct a special type of signal, the nerve impulse (action potential) that overcomes these biological constraints. Contrary to passive conducted electrical signals, action potentials of not diminish over distance because they are signals of fixed sign and location Cells capable of generating a conducting action potential, which include both nerve and muscle cells, are said to have excitable membrane. The ''Action'' in an action potentials occurs at the membrane A cell (with an excitable membrane) at rest when it is not generating impulses: the cytosol along the inside surface of the membrane has a negative electrical charge compared to the outside The difference in charges is called the resting membrane potential (the action potential is a brief reversal): in a brief instant, the inside of the membrane becomes positively charged