1. Neurons, action potential, gross neuroanatomy of the brain and spinal
cord, central and peripheral nervous system, neural control of muscle
tone and posture, synapses, transmission of nerve impulse,
neurotransmitters.
Nervous system
2. Central Nervous System Peripheral Nervous System
Brain
Spinal cord
Retina
Sensory neurons
Cluster of neurons: ganglia
Nerves, neural pathways
Autonomic nervous system Somatic nervous system
Sympathetic skeletal muscle
Parasympathetic
Enteric nervous system (independent)
Nervous system is made of nerves which can arrange in nets or networks
throughout bodies and send and receive signals
In more complex organisms nerves can cluster and form ganglia and originate
from a centre called brain
Nervous system
5. Neurons
Send signals
Electrochemical waves
Travel along AXON
Neurotransmitters
Released at synaptic junctions
Signal (excitation, inhibition, modulation)
Connections using glial cells (structural and metabolic support)
Helps make perception of outer world
6. NEURON STRUCTURE
Recieves signal
Axon
Transmits
signal to
other cells
Site of communication
with other neurons
Transmitting neuron
Recieving neuron
Release neurotransmitters
100,000 synapses in a
highly branched dendrite
7. GLIA: supporting cells
Astrocytes (stem cells)
Radial glia (stem cells)
Schwann cells (PNS)
Oligodendrocytes (CNS)
Hold neurons together
8. ION PUMPS AND ION CHANNELS MAINTAIN RESTING POTENTIAL
When cell is not transmitting signals pot is b/w -60 to -80mV (Resting cell pot)
high
high
Organic ions
high
GATED ION CHANNELS
STRECH GATED IC LIGAND GATED IC VOLTAGE GATED IC
Stretch sensing cells
Open when mech deformation
Found at synapses
Neurotransmitter
Binds to a channel
In axons, when memb pot
changes
Responsible for generating signals in the nervous system
9. Incr in magnitude of memb
pot (-92mV)
Memb is -ve on inside
Incr memb permeability to K+
Decr in magnitude of memb
pot (+62mV)
Memb is +ve on inside
Incr memb permeability to
Na+
Graded potentials: varies with degree of stimulus
Both VGIC for (1) Na+ and
(2)K+ open
ACTION POTENTIALS ARE SIGNALS CONDUCTED BY AXONS
10. Action Potential
Graded depolarization to a certain voltage: threshold
A strong stimulus which produces a depolarization that reaches the
threshold generates a different response known as Action Potential
All or none phenomenon
Independent of strength of the stimulus
Signals that carry information along axons
1-2 milliseconds: short time high frequency signals
Both Na+ and K+ channels open by depolarization
Respond independently
First Na+ (2 channnels) and then K+
11.
12. If a second depolarizing signal is provided it will be unable to trigger
an AP
This “downtime” following an AP during which a second AP cannot be
initiated is called REFRACTORY PEROID
This interval sets the maximum freq at which an AP can be generated
14. SPEED OF ACTION POTENTIAL
Axon thickness: thicker the axon faster conduction
Myelin sheath incr conduction speed since it acts as insulator
Causes incr in speed
More concentrated voltage gated channels for Na+ and K+ in a myelinated axon
at Node of Ranvier
AP is only generated at nodes
AP jumps from one node to other, depolarizes and new AP generated
SALTATORY CONDUCTION (speed is 120m/sec in myelinated axon)
15. NEURON TO NEURON COMMUNICATION AT SYNAPSE
Electrical synapse
Transmission of electrical signals to
neurons
Gap junctions allows signals to flow
from cell to cell
Chemical synapse
Transmission of chemicals signals from
neurons to neuron by use of
neurotransmitters.
They are synthesized by presynaptic
neurons and packaged into synaptic
vesicles stored in synaptic terminals
16. Direct synaptic transmission (DST):
Neurotransmistter binds to receptor and opens
channels of post synaptic cell to allow diffusion of
specific ions to postsynaptic membranes
Postsynaptic potential: change in membrane
potential of postsynaptic cell
Na and K both diffuse when channels open
Postsynaptic membrane depolarizes and brings
membrane potential towards threshold they are
known as : excitatory post synaptic potentials
(EPSPs)
Other synapse, different neurotransmitter binds
allow diffusion of only K+. When channels open
postsynaptic membrane hyperpolarizes. Such a
hyperpolarization are called Inhibitory post
synaptic potentials (IPSPs) membrane potential
away from the threshold
18. 1. DST are different than AP (all or none) because they are graded as their
magnitude varies with number of factors (eg. amt of neurotransmitter)
2. DST become smaller along the length of axon unlike AP which regenerate as
they spread
3. DST at synapse but AP at the Axon hillock; hence EPSP is too small to
generate AP
Summation effect of Postsynaptic potentials
19.
20. Indirect synaptic transmission (IST):
Neurotransmitter binds to receptor which is not a part of an ion channel
Activation of signal transduction pathway involving second messenger (cAMP) in
postsynaptic membrane
Slow onset but last longer
Nor epinephrine-receptor complex
G protein----> adenyl cyclase
ATP-----------------> cAMP
protein kinase A--------------> phosphorylates specific channel proteins in
postsynaptic membranes
G protein coupled receptors: GTPases; involved in binding and sensing receptors
outside the cell and activate signal transduction pathways, bind to ligands like
odurs, pheromones, hormones, neurotransmitters, peptides or large proteins.
Guanine nucleotide binding proteins
21. Fatigue: when excitatory synapses are repetitively stimulated, results in no of
discharges become less subsequently and lead to fatigue of postsynaptic
neurons
[inactivation of receptors of poSN]
Effect of pH on synaptic transmission
Alkalosis
Increase on pH
Incr in neuronal excitability
Incr in pH of arterial blood from 7.4
to 7.8
Leads to cerebral seizures due to
over excitability of cerebral neurons
Epileptic seizures
Overbreathing
Less CO2
Incr in pH
Acidosis
Decrease on pH
Decr in neuronal excitability
Decr in pH from 7.4 to 7.0
Leads to comatose state
In case of severe diabetes,
uremic acidosis leads to
diabetic coma
22. Effect of Hypoxia on synaptic transmission
Stopping of O2 supply can lead to inexcitability of neurons, brain blood flow
is interrupted within 3-7 sec …unconsciousness.
Effect of Drugs on synaptic
transmission
Increase excitability
Caffeine, theophylline, theobromine in
Coffee, tea and cocoa by reducing the
threshold for excitation
Strychnine : inhibits inhibitor
transmitting substances and
overexcitation
Leading to severe muscle spasm
The minimal period of time required for events
during transmission of a neuronal signal from a
presynaptic neuron to a postsynaptic neuron to
take place, even when large numbers of
excitatory synapses are stimulated
simultaneously, is about 0.5 millisecond. This is
called the synaptic delay.
24. Neurotransmitters
Acetylcholine (Ach): both in vertebrates and invertebrates. Acts as NT in PNS and CNS
Inhibitory
Excitatory type of receptor
Ach binds to ligand gated receptors at neuromuscular junction and
generates EPSP by direct post synaptic transmission
At synapse of Motor neuron
and Skeletal muscle
Nicotine can bind to the same receptors as Ach hence its physiological and
psychological effects are because of its binding affinity.
Ach released by parasympathetic neurons in cardiac muscle activates
signal transduction pathway via G coupled proteins receptors (GCPR)
1. Inhibition of adenyl cyclase
2. Opening of K+ channels in muscle membrane
3. Strength and Rate of contraction of cardiac muscle is reduced (INHIBITORY)
In skeletal muscle, Ach causes contraction and is EXCITATORY
25. Ach forms the cholinergic system in CNS (anti excitatory actions)
In PNS : acts on muscles
Ach stimulation causes
• release of epinephrine and norepinephrine from medulla via symp. Nerves
• Role in enhancing sensory perception and sustaining attention
• Role in Decision making
• Learning and short term memory
Damage to cholinergic nerve fibres: leads to loss of memory in Alzheimers
26. Enzyme (ACE)
Acetyl CoA + Choline----------------------------------- Ach
reversible
inactive
Neurotoxins: bind to ACE leading to excess Ach causing paralysis,
stopping of breathing and beating of heart
ACE inhibitors: nerve gas (Sarin and VX nerve gas), pesticides
(organophosphates and carbamates)
Also used as drugs as muscle relaxants for myasthenia gravis and
Alzheimers
Botulin toxin acts by suppressing release of Ach, causes paralysis
Venom from a black widow spider (alpha-latrotoxin) has reverse effect:
wastage of Ach and muscles begin to contract…amount depletes and
paralysis.
27. Biogenic amines (monoamines):
Derived from amino acids
Often involved in indirect post synaptic
transmission in CNS
NorE involved in PNS
Histamines: derv. of aa Histidine
Catecholamines: derv of tyrosine
Epinephrine:hormone
Nor epinephrine:hormone
Dopamine
Tryptamines
Seretonin: syn from tryptophan
Melatonin
Trace amines
Dopamine and seretonin (secreted in brain) involved in affecting, sleep, mood,
attention, learning
Imbalance of these results in several disorders and conditions and also used for
treatment. Eg.
1. Parkinsons Disease: lack of Dopamine in brain
2. Use of drugs and mescaline allows them to bind to receptors for Seretonin
and Dopamine and produce hallucinatory effects
3. Depression is treated by administration of increased conc of biogenic amines
(Seretonin and/or NorE). Prozac (Eli Lilly) incr conc of seretonin by
inhibiting its uptake after release
Neurotransmitters
A hallucination is a perception in the absence of external stimulus that has qualities of real perception
Prozac: Antidepressant with Serious Side Effects
28. Amino acids and Peptides:
Gamma amino butyric acid (GABA)
Glycine
Glutamate: NMDA (n-methyl D- asp)
glutamate receptor
Aspartate
GABA: generates IPSPs by increasing permeability of post Synaptic Memb to Cl-
Neuropeptides: short chain of aa can act as NTs
Non peptides can also act as NTs
Many neuropeptides are made by post translational modifications
Most neuropeptides work using signal transduction pathways
Substance P
Endorphins
Mediates and increase perception of pain (excitatory NT)
Natural analgesic (painkiller) dull the perception of pain
Certain receptors for opiates and morphine (like endorphins) relieve pain
By mimicking endorphins produced during physical and emotional stress, childbirth
Endorphins also decr urine output by stimulating ADH secretion, depress
respiration, and induce euphoria (as a mental and emotional condition)
Endorphins are also released from anterior pitutary hence can see the overlap b/w
endocrine and nervous system
Neurotransmitters
29. Gases
Nitric Oxide (NO)
Carbon monoxide (CO)
Act as local regulators
• NO : utilized for syn of cAMP (2ndry messenger)
• CO is synthesized by heme oxygenase and one form of it is localized in brain and
PNS.
• In brain it is used for release of Hypothalmic hormones, in PNS it act as inhibitory
NT hormone that hyperpolarizes intestinal smooth mucsle cells.
• NO is required for long term memory
NO and CO are synthesized quickly, not stored, act fast or pass on
message to secondary messenger, affect cell metabolism immediately
and degrade fast.
Neurotransmitters
30. CNS and PNS
Invertebrates: Ventral nerve cord (analogous to spinal cord) and segmented
ganglia in most
Vertebrate spinal cord runs dorsally and does not contain segmented ganglia
DORSAL EMBRYONIC NERVE CORD
VERTEBRATE CNS
Notochord
Post anal tail
Pharyngeal gill slits
Characteristic
feature of chordates
ECTODERM
Dorsal : backside
Ventral: belly side
Adults
Narrow central canal of spinal cord
Four ventricles of brain
Cerebro-spinal fluid
Drains into veins, Supply of nutrients to parts of brain and removal of wastes
Also present b/w two meninges ie. B/w layers of connective tissue behind CNS
31.
32. Gray matter: dendrites, non myelinated axons, neuron cell
bodies
White Matter: well defined bundles, tracts, large amount
of axons with myelin sheath which give a white appearance.
33. Peripheral
Nervous System
Transmits information to and from the CNS
1. Cranial nerves: nerves emerging from the brain and
terminate in regions of organs of the head and upper body.
12pairs of cranial nerves [olfactory and optic are
sensory only]
2. Spinal nerves: nerves emerging from the spinal cord and
extend to parts of the body below the head. 31 pairs of
spinal nerves
Sensory or
motor neurons
Skeletal mucsles
Respond to external stimuli
Voluntary
Controlled by spinal cord or brain stem
Regulates internal environment by
controlling smooth and cardiac muscle,
digestive, excretory, cardiovascular,
endocrine
involuntary
Arousal and energy generation
Fight or flight response
Secretion of adrenaline (epineprine)
from adrenal medulla
REST AND DIGEST
Opposite effect, calming effect and
return to self maintenance functions
Rest and digest response
Secretion of nor adrenaline or nor
epinephrine
Independent
Can be controlled by
Sym and para sym
34.
35. OLd OPie OCcasionally TRies TRIGonometry And Feels VEry GLOomy, VAGUe,
And HYPOactive.
37. Brainstem
Medulla oblongata
Pons
Mid brain
1. Responsible for sending signals via neuron cell bodies to send axons to
cerebellum and cerebral cortex
2. Release neurotransmitters like Ach, dopamine, seretonin and Nor Epi
3. Responsible for attention, alertness, appetite and motivation
Medulla: automatic and homeostatic functions. Breathing, heart,
blood vessel activity, swallowing, vomiting, digestion
Pons: similar activities and it regulates centers of medulla
Mid brain: receipt and integration of sensory information,
connects regions of mid brain to fore brain and then to Spinal
cord
Right side controls movts of left side and vice versa
Information
transmission,
Large scale
body movts
like walking
metencephalon
mylencephalon
mesencephalon
38. Brainstem
Arousal and sleep: reticular formation
Pons and medulla contain centres which regulate sleep
seretonin and melatonin is used to regulate biological clocks and sleep
patterns in animals
Learning is active during sleep
Melatonin: for treatment of jet
lag, insomnia, seasonal sleep
disorder, depression
Dietary changes (incr use of
tryptophan foods can induce
sleep like milk)
39. Cerebellum
Diencephalon
Co-ordination, error checking during cognitive, perceptual and
motor functions
Cognitive: learning, decision making, consciousness,
integrated sensory awareness of surrounding
Learning and remembering motor skills, receives
information from visual and auditory systems
Movements and balance, hand eye coordination
Damage to cerebellum loses ability to coordinate movements: eye cannot focus
Epithalamus: pineal gland and choroid plexus (CSF)
Circardian rhythm, biological clock
Thalamus: input centre for sensory info going to cerebrum and
output centre for motor info leaving cerebrum. Sorting centre
and then info sent to different areas. Regulate emotions and
arousal.
Hypothalamus:impt for homeostatic regulation,
Hunger, thirst, survival mechanism thermostat,
Sexual and mating behaviour, flight fight response pleasure
Manages endocrine system (neuroendocrine system)
metencephalon
40. Cerebrum Right and left hemisphere
Each hemi: Outer grey matter, cerebral cortex and inner white matter
Basal nuclei:neurons deep seated; involved in planning and
learning movement sequences
Damage can lead to prevention of motor commands to be
sent to muscles and render a person immobile and passive
Most complex region, main info processing, commands, integration, language
Neocortex in humans is highly convoluted, large surface area to fit in skull
Whales and porpoises have exceptionally large and convoluted neocortex
Connects left
and right side
cerebral
cortex
coordination
41. Cerebrum
Damage to one hemisphere
transfers all functions to a
to other hemisphere
Evolutionary importance
Information processing: complex
Voluntary movts and cognitive functions
Language
Speech limbic system
Emotions
Memory: long term and short term (hippocampus) practice and rehersal
Learning
43. Limbic system: cerebral pre cortex and subcortex of brain
Hippocampus: long term memory, cognition and navigation
Amygdala: significant stimulus to reward and fear and neuropsychological funcs
Decision making, formation of memory, new memory, attentional
processing, reward, pleasure and addiction
Limbic system works in co-ordination with endocrine system and ANS
Responsible for “HIGH” during sexual pleasure and during consumption
of recreational drugs. Modulated by dopaminergic neurons from limbic
system.
The L system is connected to pre frontal cortex which is attributed to
pleasure attained in solving problems.
Severing the connection by surgical procedures like LOBOTOMY for
emotional disorders patients (schizophrenia, Bipolar disorder, etc.)
become passive and lack motivation for doing anything.
44. Amygdala
• Emotional learning
• Long term memory (long term potentiation)
• Memory modulation
• Fear conditioning (features)….damage causes loss of fear…antisocial
behaviour….related to several disorders related alleviation of fear
(dissociative identity disorder, post traumatic stress disorder, phobia
• Neuropsycological activity
• Sexual orientation
• Social interaction, personal space
• Aggression
• Alcoholism and binge drinking
45. Long term potentiation (LTP) in vertebrate brain
Long term enhancement of signal transmission between 2 neurons
CELLULAR MECHNISM OF LEARNING Nobel laureate
Eric Kandel
Hippocampus region: glutamate as NT
AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
NMDA: N-Methyl-D-aspartic acid or N-Methyl-D-aspartate (NMDA)
46. Long term potentiation (LTP) in vertebrate brain
• Subject of clinical research for understanding
• Memory loss in Alzheimers and Addiction medication
• One of the phenomena of synaptic plasticity (SP)
• SP is ability of chemical synapse to change their strength by
increase of receptors or increase of NT for a longer time
• Important in long term memory
47. CNS injuries and Disorders of research interest
Nerve cell development
Neural stem cells: new neurons are continuously made; decline in old age
Exercising promotes growth of new neurons and perform better on learning tasks
Disorders
Schizophrenia: dopamine imbalance, glutamate receptors, street drugs can induce
schizophrenia like symptoms by blocking glutamate receptors
Drugs used to treat have side effects
Depression: genetic component or environmental
Bipolar disorder : maniac phase and depressive phase. Suicide is common but
some extremely creative people have had this disorder
Major depression : low mood most of the time
Prozac like drugs
Developemental disorders: Autism, Attention deficit hyperactivity disorder (ADHD)
Obssessive compulsive disorder
Personality disorders (wide spectrum)
Eating disorders (anorexia, bulimia)
Sleep disorders (insomnia, excessive sleeping)
Sexual disorders (excess and insufficient sexual activity, gender identity and many
more)
Alzheimers Disease:mental deterioration . Amyloid plaques
Parkinsons Disease: motor disorder, lack of dopamine, death of neurons inmis brain
(substantia nigra). Progressive disorder
48. Kleptomania (stealing)
Pyromania (fire setting)
Gambling
Addiction to Internet and games
Substance Abuse of recreational drugs can lead to mental disorders
