Biological Basis of Behaviour Unit 1 PDF

Course Code: UPS19CT105 Course Title: Biological Basis of Behaviour Course Transactor: Dr. Darshini Madanagopal Allied Health Sciences UNIT 1: Nature, Scope & Methods  Syllabus Unit 1: Nature, Scope and Methods Experimental Ablation, Neuroanatomical an...

Course Code: UPS19CT105 Course Title: Biological Basis of Behaviour Course Transactor: Dr. Darshini Madanagopal Allied Health Sciences UNIT 1: Nature, Scope & Methods  Syllabus Unit 1: Nature, Scope and Methods Experimental Ablation, Neuroanatomical and Neurochemical techniques, Recording the Electrical Activity in the Brain, Stimulating and Inhibiting Neural Activity Typically  Experimental Ablation Ablation involves the destruction of brain tissue followed by an assessment of subsequent changes in behaviour Ablation techniques include – Electrolytic lesions/Radio Frequency lesions – Excitotoxic lesions (kainic acid) – Neurochemical lesions (6-OHDA) 6-hydroxydopamine or is a neurotoxic synthetic organic compound used by researchers to selectively destroy dopaminergic and noradrenergic neurons in the brain. – Aspiration – Knife cuts  Evaluating the behavioral effects on brain damage Lesion = wound or injury Refer brain damage as brain lesion Experiments in which part of the brain is damaged and animal behavior is subsequently observed are called lesion studies  Ablative brain surgery is the surgical ablation by various methods of brain tissue to treat neurological or psychological disorders. "Ablation" =Latin word Ablatus = “Carried away". In most cases, however, ablative brain surgery doesn't involve removing brain tissue, but rather destroying tissue and leaving it in place. Lesions are irreversible. There are some target nuclei for ablative surgery and deep brain stimulation.  Producing Brain Lesions At the Surface Level At Sub-Cortical level Surface level - When do we do this?  Producing brain lesions At Sub-cortical regions 1. Lesion making device – RF current (radio frequency current) alternating current of a high frequency- produce heat that kills cells in the region surrounding the tip of the electrode. It destroy everything in the vicinity of the electrical tip, including the neural cell bodies and axons of the neuron that pass through the region.  Lesion Generator 2. Excitotoxic lesion: lesion produced by injecting an excitatory amino acid such as kainic acid, which kills neurons by stimulating them to death It kills neural cell bodies in the vicinity but spares the axons that belong to different neurons that happen to pass nearby  10 What a Sham. When we pass an electrode or a cannula through the brain to get to our target, we inevitably cause a small amount of damage to other areas as well. Which makes causal inferences implausible. Sham lesion is produced in the control group to avoid this problem.  Sham lesion: A placebo procedure that duplicates all the steps of producing a brain lesion except the one that actually causes the brain damage. Sometimes researchers don’t cause permanent brain damage to animals. They inject local anesthetic to the target area blocking action. 12 Stereotaxic Surgery The process by which an electrode or a cannula is precisely located and produces lesions in a brain is called stereotaxic surgery. Done with an apparatus called stereotaxic apparatus. For precise measurements of brain stereotaxic atlas is used. 13 Stereotaxic atlas is a collection of drawings of sections of the brain of a particular animal with that provide coordinates for stereotaxic surgery. 14 StereotaxicApparatus  QUESTION Would Brain Surgery hurt? 15 Stereotaxic Surgery on human brain  Neuroanatomical techniques Histological methods – Histology is the microscopic study of animal and plant cell and tissues through staining and sectioning and examining them under a microscope (electron or light microscope) – Microscope – Electron microscope Brain- imaging techniques  16 Fixation Process of maintaining natural state of specimen Types- Chemical and Physical  Physical Fixation Chemical Fixation Heat Fixation- simplest Uses organic or non-organic Microwave Fixation – solutions to maintain Speeds up fixation process. adequate morphological Freeze drying preservation Uses Chemical ‘Fixatives’  Chemical Fixation Chemical Fixation: To preserve the tissue from decomposing it is placed in a fixative chemical such as formaline.  Chemical Fixation Fixation also facilitates proper staining of tissue. Typically the ‘Fixative’ should be 20-25 times the volume of the sample / specimen. Q:So what makes a good Fixative? A:Penetrate quickly and stop tissue from shrinking. Example of good fixatives Formaldehyde Alcohol Picric Acid Potassium dicromate  17 Sectioning: A tissue is then sliced into thin sections to place under microscope Slicing is done with a microtome.  Process After the tissue is cut, the slices are attached to glass microscope slides. The slides are then put in various chemical solutions, the process known as staining. Staining is done to give contrast to the tissues under microscope to make the smaller structures clearlyvisible. The most frequently used is cresyl violet.  Electron Microscopy It is a technique for obtaining high resolution images of biological and non-biological specimens. It uses a beam of accelerated electrons as a source of illumination.  20 Tr a n s m i s s i o n electron microscope is used to see the small details of the cells such as synaptic vesicles. Electron Photomicrograph showing a section through an axodendritic synapse.  Scanning Electron Microscope 21 3 Dimensional images  Brain-imaging technologies These techniques make possible the study of both brain anatomy and patterns of brain activation in living Beings.  Quiz! EXPAND THE FOLLOWING CT CAT Scan MRI fMRI PET EEG  Imaging? ❖Computerized tomography / Computed Axial Tomography ❖Magnetic resonance imaging ❖Positron emission tomography. Computerized Tomography / CAT Tomo + Graphy Computerized tomography (CT) was the first of the new brain-imaging technologies  Computerized Tomography / CAT CT is an enhancement of the familiar X-ray procedure. Instead of producing the usual shadow imaging of a conventional X-ray, in CT an image of a horizontal slice of tissue is reconstructed. In CT, narrow X-ray beams are passed through the head in a particular cross- sectional slice from a wide variety of angles. The amount of radiation absorbed along each line is measured. From the measurements associated with each beam, a computer program can determine the density of tissue at each point in the slice.  Magnetic Resonance Imaging It is a radiology technique Uses Magnetism, radio waves and computer produced images 1997 – First MRI on a human 5 Hours (!!!) to produce 1 image  Magnetic Resonance Imaging Same as CAT Scan (Same imaging type- mathematically reconstructed image of slices of living tissue) EXCEPT it uses a very different source of information than the X- rays used in CT (Radio- freq) MRI exploits a phenomenon known as nuclear magnetic resonance, in which radio-frequency energy in a strong magnetic field is used to generate signals from a particular atom - usually hydrogen - contained within the tissue. Certain properties of the phenomenon of magnetic resonance confer great advantages to MRI as an imaging technique.  Advantages Unlike in CT, no ionizing radiation is employed. MR images have extremely fine spatial resolution, providing neuro anatomical images of exquisite detail It is possible to obtain slices at any angle, not just in the horizontal plane, as is the case with CT. Three- dimensional images of the brain may also be generated. Advanced MRI methods have recently permitted the imaging of brain function as well as structure, measuring both brain blood flow and oxidative metabolism. Soft tissue more clearly visible. No trace substance injected.  Differences between CT and MRI Similarities? – Observe inner body organs. Detect illness. Advantages of CT over MRI and vice versa.  Disadvantages? V. sensitive to head movements V. Loud because of the magnet Not v. feasible for patients with metallic implants. More expensive than CT  For our Bio (and Physics?) students! MRI magnet strength is measured in Teslas? 0.5-T to 3.0-T range The magnet field produced by the magnet in a 1.5T MRI machine is 30,000 times stronger than that produced by the Earth. fMRI  MRI vs FMRI Anatomical structure Vs. Metabolic function Focus on protons in hydrogen nuclei Vs. focus on oxygen levels High spatial resolution Vs. range resolution  Positron Emission Tomography Functional properties of the living human brain. PET involves the injection of a tracer substance labeled with a positron-emitting radionuclide. One common tracer is labeled fluorodeoxyglucose (FDG), that is taken up by cells when they need glucose for nutrition.  Over the course of a few minutes, metabolically active portions of the brain will accumulate more FDG than well less active regions. By determining where FDG is accumulating in the brain, patterns of differential brain activation can be mapped.  QUIZ! EEG = Electroencephalograph Electro + En + Cephalo + Graph What does this word mean? Literal translation?  An electroencephalograph (EEG) is the recorded electrical activity generated by the brain. In general, EEG is obtained using electrodes placed on the scalp with a conductive gel. The amplitude of an EEG signal typically ranges from about 1 uV to 100 uV in a normal adult, and it is approximately 10 to 20 mV when measured with subdural electrodes such as needle electrodes. (microvolt = 1/10,00,000 volts) It is called the 10-20 system, because the electrodes are placed at sites that are 10% or 20% of a measured length from a known landmark on the skull.  Electrodes A conductor through which electricity enters or leaves an object, substance, or region. Microelectrode / Single-unit Macroelectrode Recording Studies the function of a single neuron. Used to obtain an overall picture of Thinner than a human hair. the activity in particular regions of Ending is charged and inserted into the brain. neuron. Can’t see through skull, but can Changes in neurons documented. show activity in brain. Mostly used to study effects of neurotransmitters  Magnetoencephalography Records the Magnetic fields produced by the electric current during brain activity. SQUIDS- “Superconducting Quantum Interference Devices” Neuromagnetometers - devices that contain multiple SQUIDs. The magnetic fields are used to find the location of the neuronal sources in the brain. The resulting source location can be superimposed on an MRI for surgical planning  Magnetic Source Imaging MEG + MRI = MSI Magnetic Fields Function + MSI Structure MRI  To summarise! Types of Brain Imaging Techniques Microelectrode Examines individual neurons Examines brain activity without producing an Macroelectrode image Ex: EEG Structural Shows image of brain structure Imaging Ex: CAT scan, MRI Functional Shows image of brain activity Imaging Ex: MEG/MSI, PET Scan, fMRI  Why passively study brain activity if you can activate the neurons yourselves! 1. Electrical Stimulation 2. Chemical Stimulation 3. Optogenetic method  Optogenetic method : Optogenetics is a biological technique to control the activity of neurons or other cell types with light. (Opto + Genetic) The use of a genetically modified virus to insert light-sensitive ion channels into the membrane of particular neurons in the brain; can depolarize or hyperpolarize the neurons when light of the appropriate wavelength is applied. The method harnesses microbial proteins, known as opsins, which are light-activated proteins (channels or pumps) that permit transmembrane movement of ions. Optogenetic method : Cute or Creepy?  Question ! Is this stuff done on humans? Transcranial Magnetic Stimulation (TMS)  Quick Term Recap!! Before going to Neurochemical Methods Agonists are drugs or naturally occurring substances that activate physiologic receptors. Antagonists are drugs that block those receptors.  Neurochemical Methods Neurochemical methods can be used to determine the location of an enormous variety of substances in the brain. These methods can be used to localize neurotransmitters themselves or the enzymes that produce them.  Neurochemical Methods Organophosphate insecticides Human exposure to insecticides that contain acetylcholine agonists could cause intense, bizarre dreams and walking hallucination. The insecticide directly activated the neural circuits responsible for dreaming. Three possibilities 1. We could look for the neuron that produce acetylcholine 2. We could look for the enzyme acetylcholinesterase 3. We could look for acetylcholine receptors