An Introduction to Neuroanatomy

Prof James McCulloch : Prof of Neuropharmacology

Structure of the Lecture

Didactic Focus on Rodents and Humans The Basic Vocabulary Gross Anatomy-Finding Your Way Around the Brain Principles of Organisation Wiring Diagrams Neurotransmitter Systems

Basic Neuroanatomical Terms

Rostral=Front Caudal=Back Dorsal =Top Ventral=Bottom Medial =Middle Lateral=Side

Orientation :Planes

Rat Brain Dorsal Surface

Lateral Rostral

Medial

Caudal

Lateral

Rat Brain Horizontal Section

Lateral

Rostral

Caudal

Lateral
3H-AMPA Binding Autoradiography

Human Brain :Horizontal Plane

Rostral

Caudal

Horizontal Plane -Common in Human Brain Imaging Less Common in Rodent Research

Rat Brain Sagittal Plane Major Brain regions

Dorsal Caudal

Rostral

Ventral

Human &Rat Brain Sagittal Plane

Stereotactic Atlases-Brains on a Grid

The Best :Paxinos and Watson for Mouse and Rat

Rat:Coronal Diagramme at 5.7mm Rostral to Interaural Line

Rat:Coronal Diagramme at 10.6mmRostral to Interaural Line

Human Brain Imaging Structural Imaging and Functional Imaging

Whole brain captured Seconds/Minutes Reconstruct Any plane

Horizontal

Coronal

Sagittal

Human Brain:Multiple Horizontal Images

Most Ventral

Most Dorsal

Human Brain Multiple Sagittal and Coronal Images

Sagittal

Coronal

Transverse Planes ie Not at Right Angles(90 degrees)

Lobes of the Human Brain

Frontal-Reasoning and Motor Parietal-Sensory Temporal-Memory and Sound Occipital-Vision No Sulci in Rodent Cortex

Basic Neuronal Anatomy

Dendrites Cell Body (perikaryon) Axon (myelinated or not) Terminals Synapse

White Matter Human -60% of Brain Rat-15% of Brain

The Visual Pathway

The Visual Pathway

Functional Activation in Humans PET Imaging with 18F-DG

The Auditory Pathway

Functional Activation in Humans PET Imaging with 18F-DG

The Auditory Pathway Functional Imaging in the Rat

The Thalamus
Multiple Nuclei Reciprocal Connections with a cortical area

Major Thalamic Nuclei in Humans

Thalamus and Cerebral Cortex

Localisation of Function in Cerebral Cortex

Organisation of Cerebral Cortex Layers and Columns

Hippocampus

Hippacampus and its Connections

Cerebellum

Dopaminergic Pathways in the Rat

Dopamine containing cell bodies located in substantia nigra(A9) project rostrally to caudate nucleus etc

Dopamine Containing Cell Bodies in Substantia Nigra Degenerate in Parkinsons Disease

Reduced Synthesis of Dopamine in Caudate Nucleus-Putamen in Parkinsons Disease

PET scans of 18F-DOPA incorporation into dopamine in vivo

Connections of the Caudate Nucleus-Putamen

Serotonin (5-HT) Pathways

Serotonin Pathways
Originate in raphe nuclei Project throughout cerebral cortex

Sleep-wake cycles Mood and emotional behaviour Deficiency-depression Migraine

Noradrenaline Pathways in Brain

Originates in locus coeruleus Projects diffusely Cortex,amygdala Arousal Fight+flight Action on beta receptors

Monoamine Pathways in the CNS The Classic Targets for Drugs

Noradrenaline

Serotonin

Acetylcholine in the Brain

Choline acetyltransferase: Key enzyme in synthesis of ACh

Marked reduction in Choline Acetyltransferase in Alzheimers Disease

Reductions particularly large in Frontal & Temporal Cortices

Glutamate is the major excitatory neurotransmitter in the CNS

Multiple pathways use glutamate: Cortical association Cortico-thalamic Cortico-spinal Basal ganglia Hippocampal Cerebellar

GABA is an inhibitory neurotransmitter

GABA occurs predominately in interneurons GABA is involved in 50% of inhibitory synapses Receptors - GABAA -GABAB

Structural Imaging

Functional Imagining

Useful Neuroanatomy Resources

www.brainmaps.org www.med.harvard.edu/AANLIB/home.html www.msu.edu/~brains/humanatlas/index.html Stereotactic Atlases -Rat Paxinos G. and Watson C. Academic Press (1986) -Mouse Franklin K. and Paxinos G.Academic Press(1997)

Serotonin and Depression

Drugs that reduce 5HT produce depression like effects Lesions of Raphe Nuclei disrupt sleep cycles Brains of suicide cases have reduced 5HT

Dopaminergic Neurotransmission
Dopamine projections to the limbic system and cortex
Reward, addiction

Increased dopamine function in the frontal cortex is associated with schizophrenia

Mesolimbic Projections

Serotonin (5-HT) Pathways Serotonin projections

Originate in raphe nuclei Project throughout cerebral cortex

Sleep-wake cycles

Mood and emotional behaviour

Defficency-depression

Migraine

Dopaminergic Neurotransmission
Nigrostriatal Projections

Dopamine projections to the basal ganglia involved in movement

Rat Models of Focal Cerebral Ischaemia

Permanent MCA Occlusion Transient MCA Occlusion

ACA MCA MCA

PCA

PCA
ICA ECA BA

Electrocoagulation & section of MCA

2 hours ischaemia 22 hrs reperfusion

Diversity of Dendrites

Ischaemic Damage to Neuronal Perikarya After MCA occlusion in the Rat

Control

Ischaemia

Elevated Extracellular Glutamate Is Neurotoxic

Circle of Willis
Rat Ventral Surface MCA: Middle Cerebral Artery
ACA: Anterior Cerebral Artery

The penumbra is the tissue at risk of infarction

Perfusion gradient Normal CBF

Core

Coyle 1989

core
Penumbra Infarction

Decreased CBF

Minutes

Hours

Days
Graphic:Julien Chuquet

The Concept of the Ischaemic Penumbra Rat MCA Occlusion (1hour)

Stroke
3rd leading cause of death 60,000 deaths per annum 300,000 disabled 5% NHS costs 7% social services costs 20%NHS acute beds 25% long stay beds Multiple causes: Low blood flow damages CNS
single vessel occlusion

cardiac arrhythmia haemorrhage

Human Stroke MCA Occlusion 3Hours 1Day 11 Days

CT scan Structural Damage

SPECT Cerebral Blood Flow

Clot Busting in Stroke

Tissue Plasminogen Activator (TPA) Reopens Occluded Artery

TPA in Stroke
High Risk treatment TPA effective if given within 3 hours of occlusive stroke
single vessel occlusion

TPA causes catastrophic bleeding in cerebral haemorrhage Differentiation of haemorrhagic stroke and occlusive stroke is difficult

cardiac arrhythmia haemorrhage

Glucose Use and Blood Flow in Auditory System

Positron Emission Tomography Imaging Radioisotopes in Humans

PET scanner

Principle

Lesions of Visual Pathway Reduces Glucose Use in Brain Regions Involved in Vision

Anatomical Circuits between Caudate Nucleus and Cerebral cortex

NC/Put - Caudate Nucleus Putamen GP -Globus Pallidus

MC -Motor Cortex VL- Ventrolateral Thalamus

White Matter Human -60% of Brain Rat-15% of Brain