This document summarizes research on cholinergic transmission in the central nervous system over the past 100+ years. It discusses the identification of acetylcholine as a neurotransmitter and the techniques used to study it, including histochemistry, receptor localization, and lesion studies. It also reviews the roles of cholinergic transmission in functions like synaptic plasticity, neuronal excitability, and coordinating neuron firing. Finally, it examines the involvement of the cholinergic system in conditions like schizophrenia, autism, and epilepsy.

1. Cholinergic Transmission in CNS An Overview
Vijaya Kumar
22/8/2014

2. History
•First to be identified as neurotransmitter
•Hunt-1907
•Henry Dale-1910
•Otto Leowi-1920
•Shute and Lewis- 1960
•ChAT antibodies-1980
•Receptor structure Sakmann-1984
•Neuronal excitability
• Influences synaptic transmission
• Induces synaptic plasticity and
• coordinates firing of groups of neurons

3. More than hundred years of research!!!
Techniques used for the study:
•Acetylcholinersterase activity assay and histochemistry
•Choline acetyl transferase (ChAT) histochemistry
•Vesicular choline transporter
•Nicotinic and muscuranic receptor expressions and localization
•Nerve Growth factor-p75NGFR
•Cholinergic toxins-Ethylcholine mustard aziridinium ion (AF64A)
•Microdialysis
•Lesion studies
•Retrograde labelling studies
•Developmental disruption studies
•Electrophysiological Studies
•Knockout models

5. Newman et al, Frontiers in Behavioral Neuroscience;2012

6. Phylogeny and ontogeny of Cholinergic system

7. The evolution of the cholinergic system
Laurent Descarries & Kresimir Krnjevic (2004),Acetyl Choline in Cerebral cortex,Elsevier Publishers,Vol 145

8. Subventricular zone of the ganglionic eminence (GE) in an E14 rat
Laurent Descarries & Kresimir Krnjevic (2004),Acetyl Choline in Cerebral cortex,Elsevier Publishers,Vol 145

9. Spatiotemporal pattern of neurogenesis of cholinergic neurons in the rat
Laurent Descarries & Kresimir Krnjevic (2004),Acetyl Choline in Cerebral cortex,Elsevier Publishers,Vol 145

10. ChAT fibers in Rat Parietal cortex
Laurent Descarrie s& Kresimir Krnjevic (2004),Acetyl Choline in Cerebral cortex,Elsevier Publishers,Vol 145

11. Invitro and invivo induction of cholinergic phenotype by BMP-9
Ignacio Lopez-coviella et al, Science, 2000

12. Cholinergic receptors
•Muscarinic receptors
M1 & M2
M1 subtypes: m1, m3, m5 (Layer I, II)
M2 subtypes: m2, m4 (Layer III, V )
•Nicotinic receptors
α subunits (α2-10 )
β subunits (β 2-4 )

13. Sites of Nicotinic and Muscarinic Acetylcholine Receptors
Marina R. Picciotto et al, Neuron 76, 2012

14. Lesion studies
Barry J et al,Annual Review of Psychology; 1997

15. Outcome of lesion studies
Barry J et al,Annual Review of Psychology; 1997

16. Effects of Acetylcholine on Activity of Cortical Neurons
Marina R. Picciotto et al, Neuron 76, 2012

17. Laurent Descarrie s& Kresimir Krnjevic (2004),Acetyl Choline in Cerebral cortex,Elsevier Publishers,Vol 145

18. Effects of Acetylcholine on Hippocampal-Amygdala Stress Response
Marina R. Picciotto et al, Neuron 76, 2012

19. Cholinergic Route of Panic Disorder??
M Battaglia, Molecular Psychiatry (2002)

20. Effects of Acetylcholine on Activity of Dopamine Mesolimbic Circuit
Marina R. Picciotto et al, Neuron 76, 2012

21. Regulation of Brain states
Laurent Descarries & Kresimir Krnjevic (2004),Acetyl Choline in Cerebral cortex,Elsevier Publishers,Vol 145

22. Lesion studies of cholinergic nuclei
Laurent Descarries & Kresimir Krnjevic (2004),Acetyl Choline in Cerebral cortex,Elsevier Publishers,Vol 145

23. Intrinsic Thalamic circuitry
Laurent Descarrie s& Kresimir Krnjevic (2004),Acetyl Choline in Cerebral cortex,Elsevier Publishers,Vol 145

24. Laurent Descarries & Kresimir Krnjevic (2004),Acetyl Choline in Cerebral cortex, Elsevier Publishers,Vol 145

26. Laurent Descarrie s& Kresimir Krnjevic (2004),Acetyl Choline in Cerebral cortex,Elsevier Publishers,Vol 145

27. Vigilance states between wakefulness and sleep
S Graef et al, Psychopharmacology (2011)

28. Cholinergic transmission in Basal Ganglia
Laurent Descarrie s& Kresimir Krnjevic (2004),Acetyl Choline in Cerebral cortex,Elsevier Publishers,Vol 145

29. Role of Cholinergic neurons in Spinal cord
Ventral Horn Motor Neurons
Cholinergic interneurons
around central canal
Paul Okwudiri, UCLA Electronic Theses and Dissertations,2013

30. Cholinergic functions in Hypothalamus
•Role in Thermoregulation
•Role in Feeding behavior
•Role in endocrine and metabolic function
•Sleep wake behavior
R. D. Meyers and M. B. Waller, J. Physiol. (1973)

31. Cholinergic system in Neurodevelopmental Disorders

32. Involvement of cholinergic system in schizophrenia
• Cognitive deficits are considered to be the most incapacitating aspect of schizophrenia.
• Social functioning correlates well with some cognitive deficits in patients with schizophrenia.
• Muscarinic and nicotinic receptors are implicated in the pathology of schizophrenia.
• A subgroup of people with schizophrenia have lost 75% of their cortical muscarinic receptors.
• Modulation of nicotinic or muscarinic receptors has produced modest improvements in symptoms associated with schizophrenia.

33. Muscarinic expression in schizophrenia
Elizabeth Scarr and Brian Dean, Expert Rev. Neurother. 9(1), 73–86 (2009)

34. Miwa et al, Neuron 70, 2011

35. Cholinergic receptor expression in Autism
Perry et al, The American Journal of Psychiatry; Jul 2001; 158

36. Cholinergic regulation of Inflammation
Kevin J Tracey,Journal of Clinical Investigation, 2007

37. Cholinergic Regulation of Cerebral Blood flow
Laurent Descarries & Kresimir Krnjevic (2004),Acetyl Choline in Cerebral cortex, Elsevier Publishers,Vol 145

38. Knock out models
•β2 and α 7 knock out models
•Autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE)
•caused by mis sense mutations in either the a4 or the b2 subunit.
•who use a nicotine patch or tobacco have fewer seizures

39. Thank you