Transcript Ch 5 lec 1
Monoamines Acetylcholine Amino Acids Neurotransmitters Soluble Gases Peptides Lipids Nucleosides Figure 4.9 Acetylcholinergic Pathways in a Rat Brain REM sleep (basal forebrain) learning memory + Monoamines The Monoamines A class of amines that includes indolamine, such as serotonin; and catecholamines, such as dopamine, norepinephrine, and epinephrine. See Table 4.1 Catecholamines Indolamines Dopamine Serotonin Norepinephrine Epinephrine Figure 4.13 Dopaminergic Pathways in a Rat Brain Nigrostrial = cell bodies in substantia nigra send axons to striatum = movement (parkinson’s) Mesolimbic = VTA to limbic system including NA, AMYG, & HIP (NA important for rewarding effects of stimuli including drugs of abuse) Mesocortical = VTA to prefrontal cortex (short-term memories, planning and problem solving) Figure 4.16 Noradrenergic Pathways in a Rat Brain Increased vigilance, attentiveness to events in the environment + NE Adrenergic receptors (all sensitive to NE and E) β1- and β2-adrenergic receptors α1- and α2-adrenergic receptors All are metabotropic, coupled to G proteins that control production of second messengers All are found in various organs in addition to the brain Adrenergic receptors produce both excitatory and inhibitory effects but, in general, the behavioral effects of NE release are excitatory Figure 4.18 Serotonergic Pathways in a Rat Brain Behavioral effects are complex Regulation of mood Control of eating, sleep and arousal Regulation of pain Dreaming + 5-HT Like NE, 5-HT is released from varicosities rather than terminal buttons There are least 9 different types of 5-HT receptors 5-HT1A-1B, 5-HT1D-1F, 5-HT2A-2C and 5-HT3 all are metabotropic except the 5-HT3 receptor, which is ionotropic 5-HT3 receptor controls a chloride channel, which means it produces IPSPs Drugs that inhibit the reuptake of 5-HT (SSRIs) treat mental illness Fluoxetine – treats depression, anxiety, and OCD Fenfluramine – treats obesity + GABA Glutamate Amino Acids Glysine +Figure 4.19 NMDA Receptor decreased Increased Indirect antagonist 4 binding sites on exterior and 2 binding sites deep in ion channel •when channel is open both Na and Ca ions move inside the cell, causes depolarization •Ca also serves as 2nd messenger and activates enzymes important for learning and memory •Must also have glycine binding for channel to open •Also Mg ion must not be attached to Mg binding site •Mg repelled if membrane is partially depolarized •need glutamate & depolarization •voltage and NTS-dependent ion channel + Figure 4.20 GABA A Receptor •Barbiturates, steroids and benzodiazepines all promote activity of GABA receptor (indirect agonists) •Picrotoxin inhibits activity of GABA receptor (indirect antagonist) + Peptides Endogenous Opioids Enkephalin – one of the endogenous opioids. Opiate receptors A class of peptides secreted by the brain that act like opiates (opium, morphine, heroin). At least 3 different types: μ(mu), δ(delta) and κ(kappa) Endocannabinoids Binds with THC, the active ingredient of marijuana. Anandamide – the first cannabinoid to be discovered. 2-arachidonyl glycerol (2-AG) Nucleosides Adenosine – a nucleoside; a combination of ribose and adenine; serves as a neuromodulator in the brain. Adenosine receptors are coupled to G proteins and open potassium channels (IPSP) Caffeine – a drug that blocks adenosine receptors. + Soluble Gases Soluble Gases NO and CO Nitric Oxide (NO) – a gas produced by cells in the nervous system; used as a means of communication between cells. Released by diffusion as soon as it is produced Triggers production of second messengers (cyclic GMP) in adjacent cells Functions: Control of muscles in the wall of the intestines Dilates blood vessels in brain Stimulates the changes in blood vessels that produce penile erections May play a role in learning + Mind and Brain Methods and Strategies of Research Chapter 5 + Chapter Overview Experimental Ablation Recording and Stimulating Neural Activity Neurochemical Methods Genetic Methods + Evaluating the Behavioral Effects of Brain Damage Experimental Ablation Lesion: any type of wound or injury (generic) Ablation: A type of lesion in which a brain region is removed or destroyed. presumably, the functions that can no longer be performed are the ones the region previously controlled (a.k.a. – lesion study). (never this easy) Brain Lesion Studies Producing Brain Lesions 1. Aspiration – suck it out Only useful for surface; not common 2. Electrolytic Lesion- current through lesions 3. Radio Frequency Lesion (30kHz and above) An alternating current of a very high frequency capable of destroying neural tissue. Electrolytic lesion of LC (lower) and sham operated controls(upper) + Experimental Ablation 4. Knife cuts may damage surrounding area Used to eliminate conduction in a nerve or tract 5. Cryogenic blockade “reversible lesion” Copyright © 2006 by Allyn and Bacon Neurons near the tip are cooled until they stop firing Copyright © 2006 by Allyn and Bacon Brain Lesion Studies 7. Excitotoxic Lesion A brain lesion produced by intracerebral injection of an excitatory amino acid, such as kainic acid. Kainic or ibotenic acid – destroy cell bodies 8. Selective lesion: target a specific cell type Neural poisons (neurotoxins) selectively target specific nervous system components 6-hydroxydopamine (6-OHDA) – destroys noradrenergic and dopaminergic neurons Sham Selective NE lesion Sham Lesion All the steps of producing a brain lesion except the one that actually causes the brain damage. + Experimental Ablation 9. Reversible brain lesions Effectively anesthetize the brain region Inject local anesthetic into brain (muscimol; lidocaine) Reversible in that the effects wear off Caution: damage of injection + Stereotaxic Surgery Stereotaxic Surgery Brain surgery using a stereotaxic apparatus to position an electrode or cannula in a specified position of the brain. Requires a stereotaxic atlas to identify the location of the brain area(s) of interest. + Stereotaxic Surgery The Stereotaxic Atlas A collection of drawings of sections of the brain of a particular animal with measurements that provide coordinates for stereotaxic surgery. Correspond to frontal sections taken at various distances rostral and caudal to bregma Each page of the atlas is labeled according to the distance of the section anterior or posterior to bregma + Figure 5.3 Rat Brain and Skull Figure 5.4 Stereotaxic Atlas + Stereotaxic Atlas + Anterior-Posterior Dorsal Ventral Medial-Lateral + Sample sections from Atlas + Stereotaxic Surgery The Stereotaxic Apparatus A device that permits a surgeon to position an electrode or cannula into a specific part of the brain. Includes a head holder, a holder for an electrode (or cannula), calibrated mechanism that moves the electrode holder in measured distances along the 3 axes: anteriorposterior, dorsal-ventral, lateral-medial + Figure 5.5 Stereotaxic Apparatus Copyright © 2006 by Allyn and Bacon + Stereotaxic Surgery in Humans + Experimental Ablation To verify the precise location of the brain damage (or cannula placement, etc) Histological Methods Fixation and Sectioning Fixative – chemical such as formalin; used to prepare and preserve body tissue. Formalin – aqueous solution of formaldehyde gas Stops autolysis, hardens the very soft and fragile brain, and kills any microorganisms that might destroy it + Experimental Ablation Perfusion – process by which an animal’s blood is replaced by a fluid such as a saline solution or a fixative in preparing the brain for histological examination. Microtome – instrument that produces very thin slices of body tissues + Experimental Ablation Staining techniques are typically methods which are used to visualize specific anatomy Structural Cellular Common: Nissl Dye: cresyl stain violet Stains: Nissl bodies (mostly nuclear)