introduction to CNS, Central nervous system, neurotransmitters

1. INTRODUCTION TO
CENTRAL NERVOUS SYSTEM

2.  Organization of CNS
 Ion channels & neurotransmitter receptors
 Synapse & synaptic potentials
 Site of drug action
 Cellular organization of the brain
 Central neurotransmitters

3.  Brain
 Spinal cord
 Brain  operate through chemical
neurotransmission
 BRAIN
 The Forebrain - Cerebrum
-Thalamus
- Hypothalamus
 The Midbrain
 The Hindbrain - Cerebellum
- Pons
- Medulla oblongata

5.  Cerebrum: Largest part of brain, Surrounded by
outer cortex
 Cerebral cortex divided into 3 functional areas:
 Sensory area (sensation)
 Motor area (voluntary movements)
 ↑physical & mental activities,↑↑ Convulsions
 Association area
 Higher mental activities as consciousness,
thinking, memory, behavior.
 ill developed In animal

6.  Thalamus :
 Act as a relay station for receiving Nerve impulses &
sending to sensory areas in Cerbral cortex
 Contain pain center
 The hypothalamus:
 Act as a control center for the A N S
 Contain heat regulating, appetite centers
 The mid-brain :
 Connect cerebrum to cerebellum & Pons.

7.  Cerebellum:
 Coordinates voluntary movements such as posture,
balance, coordination, and speech, resulting in
smooth and balanced muscular activity
 The medulla oblongata:
 for passage of motor & sensory neurons between
Brain & SC
 Contain 5 vital centers :Vagal,Vasomotor,
Respiratory, Cough,
Vomiting(CTZ)

8.  BBB
 Preserve internal environment
( nutrients, NT – E,NE,Ach,5-HT,DA)
 Protect brain
–Toxic substances
– Excess NT  Adv effects
Eg: 2nd Gen Antihistaminics
L-DOPA  Dopamine

9.  Limbic system: hippocampus, amygdala,VTA
(nucleus accumbens)
 Basal ganglia: corpus striatum (caudate nucleus +
putamen + globus pallidus) and substantia nigra
 Circumventricular organs –
 Area postrema, Chemoreceptor Trigger Zone (CTZ),
 Pineal gland, Pituitary gland,
 Median eminence, Choroid plexus capillaries

10.  Neurotransmitters :
 Stimulate or inhibit postsynaptic neurons
 Neuromodulators :
 Released by neurons & astrocytes
 Slow or enhance pre or post synaptic reponses
 CO2,Adenosine, purines,PG,NO
 Neuromediators :
 Second messengers – cAMP, cGMP, IP3
 Neurotropic factors :
 CNS – neurons, astrocytes, microglia
 Tyrosine kinase linked receptors
 Cytokines, chemokines, GF ( IGF, NGF,TGF, PDGF)
 Neurohormones :
 Released into blood  act on distant target organ
 Hypothalamic hormones – Hypothalamic-pituatary portal circulation

11. Neurons & Neuroglia

18.  ACh
 Biogenic amines
 Dopamine (DA)
 Norepinephrine (NE), Epinephrine (E)
 5-Hydroxytryptamine (5-HT)
 Histamine
 Aminoacids neurotransmitters
 Glutamate & Aspartate ++
 GABA & Glycine --
 Peptides as neurotransmitters
 Nitric oxide
 Miscellaneous neurotransmitters
 Endocannabinoids
 Purines (Adenosine & ATP)

20.  CNS  C.C., cerebellum, spinal cord,
basal ganglia, limbic system
 Both muscarinic & NN receptor subtypes
 Modulate - Arousal
- Respiration
- Motor activity
-Vertigo & memory

21.  M1  Excitatory : K+ conductance
IP3, DAG
 M2  Inhibitory : K+ conductance
cAMP
 NN  Excitatory : Cation conductance

22.  Centrally acting Antimuscarinic
 Parkinson’s D/s
 Motion sickness
 Anticholinesterases
 (Tacrine, Donepezil,Rivastigmine)
 Alzheimer’s D/s

24. D2,D3,D4 # Ca2+ channels, Open K+ channels, - cAMP
Gi coupled
D2 Striatum, substantia nigra, pituatory
D3 Midbrain, N.accumbens, hypothalamus
D4 Frontal cortex, medulla, midbrain
 5 DA receptors  D1, D2, D3, D4, D5
Dopamine
receptor
Features
D1 & D5 +Adenylyl cyclase, +PIP2 , +cAMP
Gs coupled
Putamen, N.accumbens, olfactory tubercle

26.  Nigrostriatal tract
 Cell bodies in the substantia nigra project to the
striatum, where they release DA, which inhibits
GABA-ergic neurons.
 In Parkinson disease, the loss of DA neurons in
this tract leads to excessive ACh activity 
extrapyramidal dysfunction.
 DA receptor antagonists  pseudo-Parkinsonism
(reversible).
 DA agonists may cause dyskinesias.

27.  Mesolimbic-mesocortical tracts
 Cell bodies in midbrain project to cerebrocortical and
limbic structures.
 Decreased dopamine in the mesocortical projection
to the dorsolateral prefrontal cortex is postulated to
be responsible for negative and depressive symptoms
of schizophrenia.
 Nicotine releases dopamine in the mesocortical
pathways alleviating negative symptoms (self-
medication hypothesis)

28.  Tuberoinfundibular
 Cell bodies in hypothalamus project to anterior
pituitary and release DA  Decreases prolactin.
 DA agonists are used in hyperprolactinemic states.
 DA antagonists may cause endocrine dysfunction,
including gynecomastia and amenorrhea /
galactorrhea.

29.  Chemoreceptor trigger zone
 Activation of DA receptors  emesis.
 DA agonists (e.g., apomorphine) are
emetic,
 DA antagonists are antiemetic.

31. α1: Excitatory: ↓ K+ conductance,
↑ IP3, DAG
α2: Inhibitory (presynaptic): ↓ Ca2+ conductance;
Inhibitory: ↑ K+ conductance, ↓ cAMP
β1: Excitatory: ↓ K+ conductance, ↑ cAMP
β2: Inhibitory: may involve ↑ in electrogenic sodium
pump; ↑ cAMP

33.  5-HT1A: Inhibitory: ↑ K+ conductance,
↓ cAMP
 5-HT2A: Excitatory: ↓ K+ conductance,
↑ IP3, DAG
 5-HT3: Excitatory: ↑ cation conductance
 5-HT4: Excitatory: ↓ K+ conductance

34.  D/s that are influenced by changes in 5-HT
brain content :
 Depression
 Social phobia
 OCD
 Generalised Anxiety
 Schizophrenia
 Vomiting

35.  Originate from post.Hypothalamus
 Arousal  Histaminergic neurons
 Postsynaptic central H1
receptors
 Sedation  Blockade of receptors

36.  GABA as neurotransmitter
 Glycine
 Glutamate receptors

41.  NMDA receptor ( N-methyl D- aspartate)
 AMPA receptor ( A;lpha- amino-3-hydroxy-5-
methylisoxazole-4-propionic acid)
 Kainate receptor
 AP-4 receptor (1,2-diamino-4-phosphobutyrate)
 APCD receptor ( 1-aminocyclopentane-1,3-
dicarboxylic acid )

43.  Memantine – alzheimer’s
 Riluzole –amytropic lateral sclerosis
 Felbamate - anticonvulsant
 Ketamine – dissociative anesthesia
 Amantadine - antiviral and
antiparkinsonian medication

46. Oxytocin
Tachykinins
Neurotensin
Vasoactive intestinal peptide (VIP)
Opioid peptides
Neuropeptide-Y

47. THANKYOU