The Neurobiological Basis of Human Behavior

S.BENJAMIN D. VISTA, MD, DPBP, FPPA

ASSOCIATE PROFESSOR OF PSYCHIATRY

There is nothing in our minds that does not go through the senses

Objectives

To discuss the neuroanatomical structural and functional organizations of the brain system To understand the molecular and neurobiological basis of behavior.

Organization of the Nervous System

INTRODUCTORY CONCEPTS

Sensory receptors are TRANSDUCERS ONTOGENY RECAPITULATES PHYLOGENY HIGHER CENTERS INHIBIT LOWER CENTERS

Prefrontal cortex

Periaqueductal gray area

Superior colliculus Nucleus accumbens

Amygdala

Arcuate nucleus Hippocampus Locus ceruleus

Inferior colliculus

cerebellum

Ventral tegmental area

The Mesolimbic System

(James Papez, 1937)

Key words:
EXCITABILITYATION

COMMUNICATION

Limbic system

Anatomy of Neuron:
Dendrites: take input
information into neuron

Cell body: cellular metabolism,

incoming signal communicated

Axon: carries
information away from cell bodies towards output terminals

Communication

The Action Potential

Resting membrane potential: -70 mV
Depolarization Nerve Impulse Synaptic Transmission

Illustration by Lydia Kibiuk

The Action Potential

hyperpolarization

Levels of Neuroanatomical study

Histology Cytoarchitecture Behavioral Neuroanatomy

Sensory systems Motor systems Associated Units

Histology

Neurons Glial cells

Neurons

Polarized, elongated cells capable of instantaneously, intracellular communication Transmission of information

Cell body

axon
nucleus dendrites synaptic cleft

Receptors activate or inactivate ion channels within the membrane and regulate the voltage potential across the membrane passage of Ca+ alters the ion concentrations and activates the 2nd messenger cascade

transmitter gate

pore channel

transmitter

transmitter

The Simple Synapse

Pre-synaptic Post-synaptic

Synapse Neutrotransmission

The Synapse

The Synapse

Process of Synaptic Transmission

Action Potential
1.
Na+ K+

Pre-synaptic Neuron

Ca++

2. 3.Synaptic vesicle 7.reuptake

Transmission

Synapse

Neurotransmitter release

4.

Post-synaptic Neuron

5. X
6.

Na+ K+

Axonal transport of presynaptic receptor

cell body
receptors being transported receptors being inserted into membrane

axon terminal

= receptor

= enzyme
1-8
Stahl S M, Essential Psychopharmacology (2000)

Action potential instantaneous pulses of membrane depolarization myelin sheath - increase the rate of AP along the axon Synaptic cleft - AP triggers the release of chemical neurotransmitters, which enter the synaptic cleft and bind to receptors Neuronal cell bodies - gray matter Myelinated axon tracts - white matter

Glial cells - regulate the extracellular environment astrocytes - ensure synaptic communication and regulate extracellular ion concentrations oligodendrocytes - serves to insulate fibers in the fiber tracts microglia - immune system cells Cytoarchitecture relfers to the local organization of neurons 47 areas - columnar organizations - acquire specific functions

Nervous system: sensory, motor and association

Sensory systems

processes external stimuli into neuronal impulses and create an internal representation of the external world enable people to manipulate the environment and to influence others behavior through communication where the sensory inputs, representing the external world, is integrated with internal drives and emotional stimuli and in turn drive the actions of the motor units

Motor systems

Associated units

THE BASIC UNIT OF BEHAVIOR IS THE REFLEX ARC.

RECEPTOR SENSORY/AFFERENT NEURON SYNAPSE IN THE CNS MOTOR/AFFERENT NEURON EFFECTOR

Sensory systems

transforms external stimuli into neural impulses and then filter out irrelevant formation to create an internal image of the environment which serve as the basis for reasoned thought.

Sensory systems

Sensory inputs Auditory Gustatory Visual Olfactory Tactile Alteration of conscious perception through hypnosis Hypnosis - state of heightened suggestibility gross distortions of perception of any sensory modality Depend on the persons goals and emotional state

Motor systems

Brainstem Corticospinal tract Basal ganglia Corpus striatum - caudate and putamen Globus pallidus Substantia nigra Subthalamic nuclei Cerebellum Motor cortex Autonomic cortex

Brainstem

primitive systems produce gross coordinated movements of the entire body controls fine movements and dominates the brainstem Motor strip - posterior frontal lobe planned movements subcorticate matter that medicate postural tone Four distinct ganglia: striatum, pallidum, substantia nigra, subthalamic nuclei

Corticospinal tract

Basal ganglia

Corpus striatum - caudate and putamen

harbor components of both motor and associated systems plays an important role in the modulation of motor acts decreased activate is related with OCD behavior when functioning properly, acts as the gate keeper to allow the motor system to perform only those acts which are goal directed. Overactivity of the striatum - due to lack of dopaminergic inhibition - results in bradykinesia an inability to initiate movements

Globus pallidus

receives inputs from the corpus striatum and project fibers into the thalamus melanin pigment degenerates into Parkinsons disease yields ballistic movements, sudden limb jerks projectile movements

Substantia nigra

Subthalamic nucleus

Nuclei of the basal ganglia capable of initiating and maintaining the full range of useful movements Cerebellum Motor cortex Autonomic cortex

Association cortex

Basic organization of the brain Three main processing blocks 1. Brainstem and the thalamic reticular activating system 2. Posterior cortex - integrates perception and generates language 3. Frontal cortex - highest level - generates programs and executes plans

Hemispheric lateralization of function

key feature of higher cortical processing primary sensory cortices for touch, vision, hearing, smell and taste are represented bilaterally e.g. Recognition of familiar faces localization of language Limbic system responsible for generating and modifying memories and for assigning emotional weight to sensory and recalled experience
one of the nucleus of the limbic system that receives fibers from all sensory areas serve as a gate for the assignment of emotional significance to memories

Amygdala

Regional functions of the brain

Frontal lobe

Parietal lobes

Voluntary movement Language production Motor prosody Comportment Executive functions Motivation
Audition Language comprehension Sensory prosody Memory Emotion

Tactile sensation Visuospatial function Reading Calculation

Vision Visual perception

Occipital lobes

Temporal lobes

Bilateral lesions Changes in personality how persons interact with the world

Prefrontal cortex

Periaqueductal gray area Superior colliculus

Nucleus accumbens

Frontal Lobe Syndrome Slowed thinking, poor judgment, decreased curiosity, social withdrawal, irritability Apathy to sudden impulsive disinhibition May be largely unnoticed, becoming apparent only under unstructured, stressful, reallife situations Trauma, infarcts, tumors, lobotomy, multiple sclerosis, Picks disease

Amygdala

Arcuate nucleus Locus ceruleus

Inferior colliculus

Hippocampus

cerebellum

Ventral tegmental area

The Frontal Lobe

Localization of specific brain functions

Arousal Attention Memory Language Emotion

Arousal and attention

Arousal

establishment and maintenance of awake sate Brain regions: brainstem, ARAS, cortex within the brainstem - ARAS - sets the level of consciousness absence of which leads to stupor and coma maintained by an intact right frontal lobe the skill of maintaining a coherent line of thought is distributed throughout the cortex medical conditions that affect the cortex: loss of skill, confusion and delirium

Attention

Major causes of acute confusion

Infectious Metabolic

Vascular

Hypoxia Hypoglycemia Uremia Hepatic disease drugs

stroke SAH

Neoplastic Traumatic

Toxic

brain injury

Memory

Three periods with distinct anatomical correlates Immediate memory functions over a period of seconds implicit in the concept of attention and ability o follow train of thought Recent memory applies on the scale of minutes to days working memory - ability to store information and relate to cognitive information Remote memory encompasses months to years

Basic structures critical to the formation of the memory: Medial temporal lobe house the hippocampus amygdala - rates the emotional importance of an experience and to activate the level of hippocampal activity Diencephalic nuclei Basal forebrain

Hippocampus - significant site for the formation and storage of immediate and recent memories

left - efficient for forming verbal memories right - non-verbal memories

Practice makes perfect - corticalization of motor commands

memorized motor acts - activation of the median temporal lobe with practice - left parietal cortex - highly skilled acts

Causes of amnesia: alcoholism, seizures, migraine, drugs, vitamin deficiencies, trauma, strokes, tumors, infections and degenerative diseases

Diencephalon - for formation of memory dorsal medial nucleus of the thalamus mamillary bodies

Clinical disorder of memory

Alzheimers disease

most common clinical disorder of memory char. by degeneration of neurons and their replacement by senile plaques and neurofibrillary tangles impaired language comprehension and visuospatial organization - parietal lobe due to thiamine deficiency in chronic alcoholics char. by severe inability to form new memories and inability to recall

Korsakoffs syndrome

Language

Clearly demonstrates hemispheric localization of function The dominant hemisphere for language directs the dominant hand Language comprehension is processed at three levels.

Phonological processing - individual sounds Lexical processing matches the phonological input with recognized words Semantic processing - connects the words to their meaning

Emotion

Derives from basic drives: feeding, sex, pleasure, pain, fear and aggression Neuroanatomical basis: limbic system other distinct human emotions: affection, pride, guilt, pity, envy, resentment - are learned and represented in the cortex

The interplay of emotions is far beyond the understanding of neuroanatomists.

Where are the representations of the id, ego and superego? What are the pathways for ethical and moral judgements? What processes allow for beauty to be in the eye of the beholder?

Hemispheric dichotomy of emotional representation

Left hemisphere - houses the analytical mind Right hemisphere appears dominant for affect, socialization and body image Left prefrontal cortex - appears to lift mood Right prefrontal cortex - causes depression

Limbic system houses the emotional association areas which directs the hippocampus to express the motor and endocrine components of the emotional state Limbic system: Papez circuit (1937) hippocampus, the fornix, the mamillary bodies, the anterior nucleus of the thalamus and the cingulate gyrus

Neurophysiology and Neurochemistry

The study of the chemical interneuronal communication - Basic electrophysiology - Translation of the AP into chemical neurotransmission

1. Ion-Channel Linked Receptor

Modified from Figure 15-12, Page 491 from: Essential Cell Biology by Alberts et al. 1997, Garland Publishing Inc. New York, NY

(e.g) GABAA receptor

Cl-

Neuroscience Exploring the Brain 2nd Edition 2001 by M.F. Bear, B.W. Connors & M.A. Paradiso. Lippincott, Williams & Wilkins, Baltimore MD, USA. ISBN: 0683-30596-4

2. G-Protein-Linked Receptor

The receptors: 7 transmembrane segments

Modified from Figure 15-14, Page 493 from: Essential Cell Biology by Alberts et al. 1997, Garland Publishing Inc. New York, NY

Neurotransmitters
Chemical signals that flow between neurons

Chemical neurotransmission - is the process involving the release of a neurotransmitters by one neuron and the binding of the neurotransmitter molecule to a reecptor on another neuron

anti- psychotics - block D2 anti-depressants - increase the amount of serotonin or noepinephrine

Neurotransmitter synthesis
Pre-propeptide mRNA prepropeptide endoplasmic reticulum signal peptidase propeptide synaptic vesicle primary mRNA pre-pro peptide gene
1-9

inactive metabolite peptide

peptide

converting enzyme

catabolic peptidase

Stahl S M, Essential Psychopharmacology (2000)

Neurotransmitter and Human Behaviour

Biogenic Amines Dopamine (schizophrenia) Norepinephrine and Epinephrine

(mood D/O, anxiety and panic states)

Serotonin
states)

(schizophrenia and affective

Presynaptic components

Synthesis of all NT except the peptide NT which is synthesized in the cell bodies NT synthesis is influenced by inclux of Ca+, levels of cAMP and circulating hormones

Synapse

between the presynaptic and postsynaptic membranes concentrations of the NTs in the synaptic cleft are regulated by feedback inhibition of the NT release and by reuptake into the presynaptic terminal by transporter molecules

Postsynaptic Components

NTs receptors are the sites of action for many of the psychotherapeutic and psychoactive drugs principal function: to alter the electrical transmembrane potential: increase or decrease the likelihood of AP

Excitatory NTs - cause depolarization of the postsynaptic membrane

Sensitivity of receptors

no. of receptors present the affinity of the receptor for the NT efficiency with which the binding of the NT to the receptor is translated into an intraneuronal message

Types of Neurotransmitters

Biogenic amines

Dopamine Norepinephrine Epinephrine Serotonin Acetylcholine Histamine

Amino acids Peptides

Biogenic amines

All biogenic amines NT are synthesized in the axon terminal Tryptophan amino acid precursor of serotonin Tyrosine amino acid precursor of the catecholamines: D, NE, E

Dopamine

Three most important dopaminergic tracts nigrostriatal tract cell bodies in the substantia nigra corpus striatum D2 receptors in the caudate nucleus suppress the activity of the caudate nucleus caudate nucleus regulates motor acts by gating which intended acts are carried out

less - bradykinesia - Parkinsons more - tics

mesolimbic-mesocortical tract tuberoinfundibular tract

Nigrostriatal tract Mesolimbic-Mesocortical tract cell bodies in the ventral tegmental area which is adjacent to the SN, CC, and LS mediate effects of anti-psychotic drugs Tuberoinfundibular tract arcuate nucleus and the periventircular area of the hypothalamus and project to the infundibulum and the anterior pittuitary D acts as a release -inhibiting factor of prolactin in the anterior pitutitary

Serotonin

Life cycle: axon terminal

tryptophan - is the rate-limiting function dietary variations:

low: irritability, hunger high: sleep, relieve anxiety, increase a sense of well-being

Major site: upper pons and midbrain, median and dorsal raphe nuclei, the LC and postrema

neurons project to the BG, LS, and CC

SEROTONIN IN THE MODULATION OF ACTIVITY OF DOPAMINERGIC NEURONS

JCPSP 2006, Vol. 16 (8): 556-562

Norepinephrine and Epinephrine

Noradrenergic and the adrenergic system Life cycle Tyrosine hydroxylase tyrosine dopamine CNS noradrenergic tracts project into the locus ceruleus in the pons axons project through the medial forebrain bundle in the CC, LS, thalamus and hypothalamus

Amino acid

Contain the building blocks of protein Brain: glutamate and aspartate Two major AA: GABA- Gamma-aminobutyric acid - inhibitory amino acid (IAA); monocarboxylic amino acid Glutamate -excitatory amino acid (EAA); dicarboxylic amino acid several anti-convulsants act through the GABAergic mechanisms

Glutamate

synthesized from glucose and glutamine in the presynaptic neuron terminals and stored in the synaptic vesicles primary NT in cerebellar granule cells, the striatum, the cells of the hippocampus its release is stimulated by nicotine Glutamate receptors: N-methyl-D-aspartate (NMDA) receptor plays an essential role in learning and memory as well in psychopathology

GABA

found most exclusively in the CNS and does not cross the BBB midbrain and diencephalon, less in the cerebral hemispheres, the pons, and the medulla synthesized from glutamate by the rate limiting enzyme glutamic acid carboxylase (GAD) which requires pyridoxine (Vit. B6) as cofactor is the primary NT in intrinsic neurons that function as local mediators for the inhibitory feedback loops

Peptides
refers to the chemical bond between the carboxylic acid group and the amino group of adjacent amino acids in a protein differ from other NT because they are manufactured in the cell body may serve as neuromodulary role at some synapses

Thank you very much!