SYNAPTIC TRANSMISSION “We are blessed with the tools, let us carve ourselves … …” SYNAPTIC TRANSMISSION Dr. B. M. Palan, M.D., D.Clin.Hypno. (USA) INSTITUTE F0R MIND-BODY HEALING, HEALTHY LIVING & REALIZING HUMAN POTENTIAL Shrenik Park Char Rasta, Productivity Road, Vadodara 390 020 Phone: (0265) 233 58 54 E-mail: drpalan@gmail.com www.drpalan.com

Electrical and Conjoint S Y N A P S E The junction where the axon of one neuron (Presynaptic neuron) terminates on the dendrites, soma or axon of another neuron (Postsynaptic neuron) Types of Synapses Chemical Electrical and Conjoint Through Neurotransmitters Almost all synapses in human C.N.S. Around 40 transmitters Through Gap junctions Only a few In smooth & cardiac muscles.

Functional Anatomy: Ends of presynaptic terminals form terminal buttons / synaptic knobs. Knobs contain many mitochondria and vesicles. Vesicles contain packets of neurotransmitter. Types: (1) Axodendritic, (2) Axo-axonal and (3) Axo-somatic. Synaptic cleft – 30 to 50 nm wide. Postsynaptic membrane contains excitatory or inhibitory receptors. In human CNS, about 10ⁿ (n=14) synapses.

Synaptic Transmission: 1 Ca++ influx 3 2 Synthesis of transmitter in the soma and its transport to the terminal knob. Storage of transmitter in vessicles. Arrival of impulse causing Ca++ influx. 4 6 5 4. Release of transmitter by exocytosis. 5. Excitatory or Inhibitory Postsynaptic Potentials. 6. Reuptake of neurotransmitter.

Electrical Events at Synapse: Studied in spinal motor neurone. Excitatory Postsynaptic Potentials (EPSP) – - Single stimulus of one synaptic knob > After a synaptic delay of 0.5 ms > Opening of voltage-gated Na+ channels > A local and graded depolarizing potential produced in postsynaptic membrane > excitability to other stimuli is increased. - EPSPš are summated to produce Action Potential (AP). - Spatial summation: Activities in many synaptic knobs at the same time. - Temporal summation: Repeated afferents in a single knob causing new EPSP before the decay of previous EPSP.

Electrical Events at Synapse: (contd.) Inhibitory Postsynaptic Potentials: (IPSP) - Single stimulation of some presynaptic fibers > Opening of Clˉ channels > Influx of Clˉ > Local hyperpolarizing potential > Decreased excitability to other stimuli. - Spatial and Temporal summation of IPSPš > Postsynaptic inhibition. When the algebraic sum of EPSPš and IPSPš reach 10–15 mV, firing level, a propagated and ‘all or none’ type of Action Potential results at the Axon Hillock.

Properties of Synaptic Transmission: One-Way Conduction Presynaptic to postsynaptic neurons. Transmitter is present only in presynaptic terminals. Convergence & Divergence Terminals from around 100 neurons converge on one postsynaptic neuron and a single neuron diverges its information to around 100 postsynaptic neurons. Form basis for several properties of synapse. 3. Postsynaptic Inhibition Direct inhibition due to IPSP through inhibitory transmi. 4. Presynaptic Inhibition Through axo-axonal synapses reduce release of excitatory transmitter.

‘C’ stimulated repeatedly, ‘Y’ and ‘Z’ both will discharge. 5. Summation If ‘A’ & ‘B’ are stimulated at the same time > ‘X’ develop EPSP at two places > Spatial summation. Subliminal Fringe ‘Y’ do not fire but its excitability is increased. It is in subliminal fringe zone. A Occlusion ‘B’ stimulated repeatedly, ‘X’ and ‘Y’ both will discharge due to Temporal summation. ‘C’ stimulated repeatedly, ‘Y’ and ‘Z’ both will discharge. X B Y C Z ‘B’ & ‘C’ stimulated repeatedly simultaneously, ‘X’, ‘Y’ & ‘Z’ (only three) will discharge (and not four).

8. Fatigue Upon repetitive stimulation of excitatory synapses at a rapid rate, the discharge rate by postsynaptic neuron becomes progressively less. Fatigue is mainly due to exhaustion of transmitter substance.

SYNAPTIC TRANSMITTERS Neuropeptide, Slowly Acting Small-Molecule Rapidly Acting Neuropeptide, Slowly Acting Cause acute responses: Transmission of sensory or motor impulses. Cause more prolonged actions: Long-term changes in numbers of receptors, long-term opening or closure of ion channels, changes in number of synapses. Synthesized in the cytosol of presynaptic terminal. Synthesized in the neuronal cell body by ribosomes. Vesicles recycled. Vesicles autolyzed.

Small-Molecule Rapidly Acting Transmitters: Class II Norepinephrine Epinephrine Dopamine Serotonin Histamine Class I Acetylcholine Class III Gama-aminobutyric acid Glycine Glutamate Aspartate Class IV Nitric Oxide (NO)

Neuropeptide, Slowly Acting Transmitters: Hypothalamic R. H. T.R.H. L.H.R.H. Somatostatin Peptides acting on Gut & Brain Leucine enkephalin Methionine enkephalin Substance P Gastrin Cholecystokinin Vasoactive intestinal polypept. Nerve growth factor Neurotensin Insulin Glucagon Pituitary peptides A.C.T.H. ß-Endorphin ά-M.S.H. Thyrotrophin G.H. Vasopressin Oxytocin From other tissues Angiotensin II Bradykinin Calcitonin