🧪Biophysical Chemistry Unit 14 – Biophysics of Neuroscience

Key Concepts and Principles

• Neuroscience studies the nervous system, including the brain, spinal cord, and peripheral nerves
• Neurons are the fundamental units of the nervous system that process and transmit information
• Neurons communicate with each other through electrical and chemical signals
• The structure of neurons, including the soma, dendrites, and axon, enables them to receive, integrate, and transmit signals
• Neuronal signaling involves changes in membrane potential, which is the difference in electrical charge between the inside and outside of the cell
• Ion channels are proteins embedded in the neuronal membrane that allow specific ions to pass through, regulating the membrane potential
• Action potentials are rapid, transient changes in membrane potential that allow neurons to transmit signals over long distances
• Synapses are specialized junctions between neurons where information is transmitted from one neuron to another through chemical neurotransmitters or electrical signals

Neuronal Structure and Function

• Neurons are highly specialized cells that are the building blocks of the nervous system
• The soma, or cell body, contains the nucleus and other organelles necessary for cellular function
• Dendrites are branched extensions of the soma that receive signals from other neurons
  • Dendritic spines are small protrusions on dendrites that increase the surface area for synaptic connections
• The axon is a long, thin extension of the neuron that transmits signals to other neurons or target cells
  • Axons are often covered in a myelin sheath, which insulates the axon and increases the speed of signal transmission
• Neurons can be classified into three main types: sensory neurons, motor neurons, and interneurons
  • Sensory neurons detect stimuli from the environment and transmit signals to the central nervous system (brain and spinal cord)
  • Motor neurons transmit signals from the central nervous system to muscles or glands, initiating movement or secretion
  • Interneurons are located within the central nervous system and form connections between sensory and motor neurons, enabling complex processing and integration of information
• Glial cells, such as astrocytes and oligodendrocytes, provide support, protection, and insulation for neurons

Membrane Potential and Ion Channels

• The neuronal membrane is a selectively permeable barrier that separates the intracellular and extracellular environments
• The membrane potential is the difference in electrical charge between the inside and outside of the neuron, typically around -70 mV at rest (resting membrane potential)
• The resting membrane potential is maintained by the unequal distribution of ions, primarily potassium (K+), sodium (Na+), and chloride (Cl-), across the membrane
• Ion channels are proteins that span the neuronal membrane and allow specific ions to pass through
  • Voltage-gated ion channels open or close in response to changes in membrane potential
  • Ligand-gated ion channels open or close in response to the binding of specific neurotransmitters or other molecules
• The movement of ions through channels is driven by their electrochemical gradients, which are determined by the concentration difference and electrical potential difference across the membrane
• The sodium-potassium pump (Na+/K+ ATPase) actively transports Na+ out of the cell and K+ into the cell, maintaining the concentration gradients necessary for neuronal signaling
• Leak channels allow ions to passively flow across the membrane, contributing to the resting membrane potential

Action Potential Generation and Propagation

• An action potential is a rapid, transient change in the membrane potential that allows neurons to transmit signals over long distances
• Action potentials are generated when the membrane potential reaches a threshold value, typically around -55 mV
• The rising phase of the action potential is caused by the opening of voltage-gated Na+ channels, allowing Na+ to flow into the cell and depolarize the membrane
• The falling phase of the action potential is caused by the inactivation of Na+ channels and the opening of voltage-gated K+ channels, allowing K+ to flow out of the cell and repolarize the membrane
• After the action potential, there is a brief refractory period during which another action potential cannot be generated, ensuring unidirectional signal propagation
• Action potentials are propagated along the axon by the sequential opening of voltage-gated Na+ channels, which depolarizes adjacent regions of the membrane
• Myelination of the axon by oligodendrocytes or Schwann cells increases the speed of action potential propagation by allowing the signal to jump between gaps in the myelin sheath (nodes of Ranvier)

Synaptic Transmission

• Synapses are specialized junctions between neurons where information is transmitted from the presynaptic neuron to the postsynaptic neuron
• Chemical synapses are the most common type of synapse, where neurotransmitters are released from the presynaptic terminal and bind to receptors on the postsynaptic cell
  • Neurotransmitters are stored in synaptic vesicles in the presynaptic terminal
  • When an action potential reaches the presynaptic terminal, it triggers the opening of voltage-gated Ca2+ channels, allowing Ca2+ to flow into the cell
  • The influx of Ca2+ causes synaptic vesicles to fuse with the presynaptic membrane and release neurotransmitters into the synaptic cleft
  • Neurotransmitters diffuse across the synaptic cleft and bind to receptors on the postsynaptic cell, causing either excitatory or inhibitory effects depending on the type of neurotransmitter and receptor
• Electrical synapses are less common and involve direct electrical coupling between neurons through gap junctions
  • Gap junctions are channels that connect the cytoplasm of adjacent cells, allowing ions and small molecules to pass directly between them
  • Electrical synapses enable rapid, bidirectional communication between neurons and are important for synchronizing neuronal activity
• Synaptic plasticity refers to the ability of synapses to strengthen or weaken over time in response to activity, which is thought to be the basis for learning and memory
  • Long-term potentiation (LTP) is a persistent increase in synaptic strength that occurs in response to high-frequency stimulation
  • Long-term depression (LTD) is a persistent decrease in synaptic strength that occurs in response to low-frequency stimulation

Neuronal Networks and Signaling

• Neurons are organized into complex networks that enable the processing and integration of information
• Neuronal circuits are groups of interconnected neurons that perform specific functions, such as sensory processing, motor control, or decision making
• Feedback loops are circuits in which the output of a neuron influences its own input, either directly or through intermediate neurons
  • Positive feedback loops amplify signals and can lead to sustained activity or oscillations
  • Negative feedback loops dampen signals and can lead to stability or homeostasis
• Neuromodulators are substances that modify the activity of neuronal circuits by altering the properties of neurons or synapses
  • Examples of neuromodulators include dopamine, serotonin, and norepinephrine
  • Neuromodulators can influence neuronal excitability, synaptic transmission, and plasticity
• Neuronal oscillations are rhythmic patterns of activity that emerge from the interactions between neurons in a network
  • Different frequency bands of oscillations, such as theta (4-8 Hz), alpha (8-12 Hz), and gamma (30-100 Hz), are associated with specific cognitive functions or states
  • Neuronal oscillations are thought to play a role in synchronizing the activity of distant brain regions and facilitating information transfer

Experimental Techniques in Neuroscience

• Electrophysiology techniques are used to measure the electrical activity of neurons
  • Patch-clamp recording involves using a glass micropipette to measure the currents flowing through individual ion channels or the membrane potential of a single neuron
  • Extracellular recording involves placing electrodes near neurons to measure the collective activity of many neurons simultaneously
  • Electroencephalography (EEG) and magnetoencephalography (MEG) are non-invasive techniques that measure the electrical or magnetic fields generated by neuronal activity at the scalp
• Imaging techniques are used to visualize the structure and function of the nervous system
  • Fluorescence microscopy uses fluorescent dyes or genetically encoded fluorescent proteins to label specific neurons or molecules and visualize their localization or activity
  • Calcium imaging uses fluorescent calcium indicators to measure changes in intracellular calcium concentration, which is an indirect measure of neuronal activity
  • Magnetic resonance imaging (MRI) uses strong magnetic fields and radio waves to generate detailed images of brain structure
  • Functional MRI (fMRI) measures changes in blood oxygenation that occur in response to neuronal activity, allowing for the mapping of brain function
• Optogenetics is a technique that uses light to control the activity of specific neurons that have been genetically modified to express light-sensitive ion channels or pumps
  • Optogenetics allows for the precise spatial and temporal control of neuronal activity, enabling researchers to investigate the causal relationships between neuronal activity and behavior
• Genetic and molecular techniques are used to study the role of specific genes, proteins, and signaling pathways in neuronal function
  • Transgenic animals, such as mice or fruit flies, are genetically modified to express or lack specific genes, allowing researchers to study the effects of these genes on neuronal development, function, and behavior
  • RNA interference (RNAi) and CRISPR/Cas9 are techniques used to selectively silence or edit genes, respectively, enabling the study of gene function in neurons

Applications and Current Research

• Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, are characterized by the progressive loss of neurons and are a major focus of neuroscience research
  • Researchers are investigating the molecular and cellular mechanisms underlying these diseases, as well as developing new diagnostic tools and therapeutic strategies
• Psychiatric disorders, such as depression, anxiety, and schizophrenia, are thought to involve disruptions in neuronal signaling and network function
  • Neuroscience research is aimed at understanding the neural basis of these disorders and identifying new targets for pharmacological or behavioral interventions
• Brain-machine interfaces (BMIs) are devices that enable direct communication between the brain and external devices, such as computers or prosthetic limbs
  • BMIs have the potential to restore sensory, motor, or cognitive functions in individuals with neurological disorders or injuries
  • Current research focuses on improving the accuracy, reliability, and long-term stability of BMIs, as well as developing new applications for this technology
• Neural plasticity and learning are active areas of research, as understanding the mechanisms underlying these processes could have implications for education, rehabilitation, and the treatment of learning and memory disorders
  • Researchers are investigating the molecular and cellular basis of synaptic plasticity, as well as the role of neuronal oscillations and neuromodulators in learning and memory
• Computational neuroscience uses mathematical models and computer simulations to study the function of neurons, networks, and brain systems
  • Computational models can help to generate testable hypotheses, interpret experimental data, and provide insights into the principles underlying neuronal information processing
  • Current research in computational neuroscience includes the development of large-scale brain models, the study of neuronal network dynamics, and the application of machine learning techniques to neuroscience data