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A fresh brain with dura removed. Note the numerous superficial blood vessels running in the arachnoid. If we strip off the meninges we see the brain has a heavily folded surface or cortex (in latin: cortex =bark) The outwardly rounded ridges of cortex are GYRI (singular GYRUS) The grooves between the gyri are SULCI (singular SULCUS) The two main sulci are also known as fissures. These are the central sulcus (fissure) between the frontal and parietal lobes, and the lateral sulcus (fissure) between the frontal and temporal lobes Recall that the main bones of the cranium are the frontal, parietal, occipital and temporal. Frontal bone Zygomatic arch parietal bone Occipital one Temporal bone The forebrain (cerebrum) can be divided into lobes that rest in the corresponding cranial fossa. The frontal lobe lies under the frontal bone in the anterior cranial fossa, the temporal lobe lies under the temporal bone in the middle cranial fossa and the occipital lobe lies under the occipital bone in the posterior cranial fossa, along with the cerebellum. The parietal lobe lies under the parietal bone. The cerebellum (little brain) lies below the occipital lobe. It has much thinner gyri than the cerebrum Note appearance of cerebellum; the gyri are thinner and straighter than in cortex Most of the gyri and sulci have individual names but for now we only need to remember the central and lateral sulci. Inside the lateral fissure there is a hidden area of cortex, the insula or ‘Island of Reil’. Before we can investigate the interior of the brain by cutting it up we need to define the planes of the brain that we will cut (section) in. The coronal plane is also known as the frontal plane Ggoing to a higher horizontal (axial) plane is going rostral. Going down towards the spinal cord and cauda equina is going caudal. This is a brain cut in the frontal plane. Unstained brain tissue shows up as grey (actually pinky-grey) and white matter Staining the brain tissue is essential to differentiate structures. In this stain cell bodies are stained blue. Thus the cortex can be seen to contain large numbers of nerve cell bodies Grey matter = cell bodies & processes White matter = axons Nowadays MRI enables us to see a histology-like picture in the living brain. Stained post-mortem Living The corpus callosum is the most important landmark in the brain. It is a bridge of axons that joins the two hemispheres and allows communication between them. Corpus Callosum The corpus callosum is very easy to identify in the midsagittal plane (below). Corpus callosum is easy to see on an MRI Underneath the anterior part of the corpus callosum we can see the lateral ventricles Note that the corpus callosum folds back on itself rostrally. This region ends in the anterior commissure ‘Folded back’ region Anterior commissure CRITERIA n n n n n NT found in axon terminals NT released by action potentials Synthesis identified External application mimic normal Response Pharmacology same for normal and externally applied NT ~ Lock & Key Model n n n NT binds to receptor NT = key Receptor = lock Receptor changes shape determines if EPSP or IPSP receptor subtypes NOT NT ~ n n ligand binds to receptor activation: + or ~ NT Receptor A n n Same NT can bind to different -R different part of NT ~ NT Receptor A Receptor B Specificity of drugs Drug A Receptor A Drug B NT Receptor B Acetylcholine - ACh n n n n n Most abundant NT in Peripheral N.S. l also found in Central N.S. Precursor = choline nutrient Degraded by acetylcholinesterasel AChE Membrane bound - pre- & postsynaptic Nicotinic receptor - ionotropic Muscarinic receptor - metabotropic ~ Acetylcholine Synthesis choline acetyltransferase choline + acetyl CoA ACh + CoA Ach - Distrubution n Peripheral N.S. n Excites somatic muscle n Autonomic NS Ganglia Parasympathetic NS Neuroeffector junction n Central N.S. - widespread Hippocampus Hypothalamus ~ Cholinergic Agonists n n Direct l Muscarine l Nicotine l small doses Indirect l AChE Inhibitors ~ AChE inhibitors n n n Physostigmine Organophosphates - irreversible l DFP l Soman & Sarin l Malathion* Agonist or Antagonist? indirect agonist ~ Cholinergic Antagonists n n Direct Nicotinic - Curare Muscarinic - Atropine Scopolamine Indirect Botulinum Toxin Black Widow Spider Venom ~ ACh Botulinum toxin A BWSV AChE N M curare atropine AChE Monamines n n n Amino acid precursors l single amine group 2 groups Catecholamines - catechol ring Indolamine - indole ring Affected by many of same drugs ~ Monoamines n Catecholamines Dopamine - DA l Dopaminergic Norepinephrine - NE l Noradrenergic Epinephrine - E l Adrenergic ~ n Indolamines Serotonin - 5-HT l Serotonergic Monoamines n n Terminated by... reuptake monoamine oxidase - MAO catechol-O-methyltranferase - COMT also in liver Reserpine ---> leaky vesicles depletes monoamines ~ Monoamines MAO Reserpine A COMT MAO Indirect Monoamine Agonists n n MAOIs Iproniazid Reuptake blockers l Tricyclic antidepressants Imipramine Desipramine Cocaine & Amphetamine ~ Dopamine n n n n n Only in central nervous system mostly inhibitory systems Reward Schizophrenia Movement l Nigrostriatal Pathway At least 5 DA-R types: D1, D2, etc. ~ Dopaminergic Drugs n n Agonist l L-dopa Antagonists l Chlorpromazine D1 l Haloperidol D2 ~ Dopamine Synthesis tyrosine hydroxylase Tyrosine DOPA decarboxylase DOPA DA Norepinephrine n n n Peripheral N.S. l Sympathetic neuroeffector junction l Adrenal glands Central N.S. l Hypothalamus l Locus coeruleus Alpha & Beta receptor subtypes l NEa & NEb ~ Noradrenergic Drugs n n Agonists l Mescaline l Ephedrine Antagonist l Propranalol l beta receptors ~ Norepinephrine Synthesis tyrosine hydroxylase Tyrosine DOPA decarboxylase DOPA dopamine b hydroxylase DA NE Serotonin n n n n NOT a catecholamine Peripheral 98% in blood & smooth muscle Central N.S. Raphe nucleus Hypothalamus R subtypes: 5HT1 & 5HT2 ~ Sertonergic Drugs n Agonists l SSRIs Selective Serotonin Reuptake Inhibitors l l Buspirone MDMA Ecstacy ~ Sertonergic Drugs n n Antagonists l Psilocybin l LSD in CNS Inverse agonist l ketanserin ~ Serotonin Synthesis tryptophan hydroxylase Tryptophan 5-HTP decarboxylase 5-HTP 5-HT Gamma-aminobutyric acid n n n n GABA - GABAergic Major NT in brain inhibitory system Receptor subtypes GABAA - controls Cl- channel GABAB - controls K+ channel Precursor = glutamate ~ GABAergic Drugs Agonists Benzodiazepines Barbiturates Ethyl alcohol (ETOH) Antagonists Picrotoxin Inverse agonist Ro 15-4513 ß CCM ~ GABA Synthesis & Reuptake From Krebs cycle metabolism of glucose in mitochondria From Glial cells GABA ---> Glutamate ---> Glutamine Glutamine into neurons After release GABA back into glia ~ GABA Synthesis glutamic acid decarboxylase Glutamate GABA Neuropeptide Chains of amino acids Synthesis in soma Often neuromodulators alters sensitivity of neurons slower, longer-lasting effects Substance P - pain signaling Endorphins - analgesia, euphoria ~ Endorphins Opioids Dynorphin met-enkephalin leu-enkephalin Beta-endorphin Receptor subtypes: mu1, mu2, kappa, delta, omega ~ Endorphins (cont.) Agonists morphine heroin codeine Antagonists naloxone naltrexone ~ Other NTs Excitatory amino acids Glutamate & Aspartate Histamine Inflammatory Response Nitric Oxide - It’s a gas Carbon Monoxide? Anandamide ligand for THC-R ~ Why would anyone want to be a neuroscientist? The scientific study of the nervous system and its relationship to cognition and behaviour. Cognitive Neuroscience Neuropathology Neuropsychology Molecular neurobiology Neuroimagery Neurosciences Neurophysiology Neuroanatomy Neuroendocrinology Neuropsychopharmacology Nervous System Peripheral + Cranial nerves Central Brain Spinal Cord Somatic (intrinsic sensing) Autonomic (extrinsic sensing) Associative Learning Mechanisms • Classical Conditioning • Discovered by Ivan Pavlov (1920s) • Passive learning • Operant Conditioning • Discovered by B.F. Skinner (1960s) • Active learning Types of Memory Explicit (conscious) Generic Episodic Implicit (unconscious) Procedural Dispositional How is the Brain studied? • Case Studies • Gene Splicing • Imaging – PET – EEG (electrical current detection) • Transcranial Magnetic Stimulation (causes temporary disruption of a brain region) – MRI – fMRI – CAT How is learning and memory enabled? • Signal Transduction: – Inter-Neuron communication occurs via Neurotransmitters at the synaptic gap • Neural Plasticity: – Through experience, Neurons can change the way they function • Long Term Potentiation: – Cellular mechanism through which associations can be detected and recorded in the brain Stage Theory of Memory Maintenance Attention Rehearsal Encoding Sensory Input Sensory Memory Working Memory LTM Indefinite duration Retrieval