Click here to load reader

Volume neurotransmission

  • View
    178

  • Download
    1

Embed Size (px)

Text of Volume neurotransmission

  1. 1. Volume Neurotransmission 1 Devashish Konar MD Consultant Psychiatrist Mental Health Care Centre, Kolkata, India Mob: +91 9434009113 +91 9732221712 Presented at ANCIPS 2015, Hyderabad
  2. 2. SOME NEUROTRANSMISSION DO NOT NEED A SYNAPSE AT ALL Neurotransmission without a synapse is called volume neurotransmission. Chemical messengers sent by one neuron to another can spill over to sites distant to the synapse by diffusion. Thus ,neurotransmission can occur at any compatible receptor within the diffusion radius of the neurotransmitter, like transmission radius of cellular telephones. Here neurotransmission occurs in chemical puffs. 2
  3. 3. HISTORY The concept of volume transmission as an important mode of chemical communication in the brain was introduced in the 1980s. New techniques like receptor autoradiography and immunohistochemistry allow detailed mapping of the locations of neurotransmitters. Findings indicate that active substances must be getting to receptors in some manner other than release from an adjacent terminal. 3
  4. 4. NONSYNAPTIC RELEASE OF NTs Mapping studies have identified axon terminals without postsynaptic specializations. Also, varicosities containing granules filled with monoamine NTs have been localized, not only in axon terminals, but also in other portions of neurons e.g., dendrites, soma, non-terminal axon segments. These findings support the possibility of non synaptic release of NTs into the ECS. 4
  5. 5. SLOWER TONIC CHANGES Volume transmission is an important mode of action for other Neurotransmitters e.g., glycine, glutamate, GABA. Many neuroactive substances e.g., glial transmitters, peptides, nitric oxide, neurosteroids are also released into the ECS. The location of a receptor, compared with the source of the neuroactive substance, is likely to be very important in determining activation. Thus, they are more likely to signal slower (tonic) changes that are occurring over a larger area. 5
  6. 6. 6 RADII OF NEUROTRANSMISSION QUANTAL RELESE AT SINGLE SYNAPSE LOW AFFINITY RECEPTORS FOR VOLUME TRANSMISSION HIGH AFFINITY RECEPTORS FOR VOLUME TRANSMISSION
  7. 7. MEDICINES DONT ACT ONLY THROUGH SYNAPSE Chemically addressed nervous system is particularly important in mediating the actions of drugs that act at various neurotransmitter receptors. Drugs will act wherever there are relevant receptors, and not just where such receptors are innervated with synapse by the anatomically addressed nervous system. Modifying volume neurotransmission may indeed be a major way in which several psychotropic drugs work in the brain. 7
  8. 8. LOCAL VOLUME TRANSMISSION At the local level, volume transmission occurs via movement of neuroactive substances through the interstitial fluid that fills the ECS. The ECS, which occupies about 20% of the tissue volume, has a very complex, three-dimensional structure. Most signaling by volume transmission via the ECS is short-distance, particularly within gray matter. It has been suggested that the highly linear nature of white-matter tracts may provide a faster route for interstitial fluid movement than occurs in gray-matter areas. 8
  9. 9. DISTANCE VOLUME TRANSMISSION It was demonstrated in the 1980s that a tracer introduced into the cerebrospinal fluid (CSF) quickly distributed into the brain parenchyma, outlining the microvasculature. Transport within the CSF potentially allows neuroactive substances rapid access to areas of the brain distant from their point of entry into the CSF. The PVS may provide a mechanism for coordinated changes in activity across multiple areas. It has been proposed that distribution by this route of CSF containing neuroactive substances is important for onset and maintenance of specific behavioral or motivational states (e.g., fear, appetite, mood, circadian rhythms). Overall, this system provides a path by which substances can be both circulated throughout and removed from the brain parenchyma. 9
  10. 10. 10 A TRACER INTRODUCED INTO THE CEREBROSPINAL FLUID
  11. 11. 11 MICROVASCULAR SYSTEM
  12. 12. CLEARANCE OF TOXINS DURING SLEEP A recent animal study reported that the rate of flow was most rapid during sleep, slowing abruptly when animals were awakened. This was a result of a reduction in the volume fraction of the ECS, which decreased from about 22%24% (asleep or anesthetized) to about 13%15% (awake). As would be predicted, clearance of substances was much faster during sleep, when the ECS was largest. These results suggest that one important function of sleep is efficient clearance of toxins and wastes from the brain by this pathway. 12
  13. 13. IMPAIRED CLEARANCE LEADING TO PATHOLOGY Any diminution in this flow through the ECS could impair clearance of solutes (e.g., amyloid beta), and this has been proposed as an important pathophysiological mechanism for several neurodegenerative diseases. It may also contribute to sequelae of low-level brain injury (microinfarction, mild traumatic brain injury). These conditions may trigger a prolonged widespread reactive gliosis and/or focal disruption of vascular perfusion. Overall, this system provides a path by which substances can be both circulated throughout and removed from the brain parenchyma. 13
  14. 14. VOLUME TRANSMISSION IN UNDERSTANDING THE PATHOLOY Volume transmission also provides a route for toxic substances in the blood or CSF to reach the brain parenchyma. This route has been implicated in both multiple sclerosis and viral encephalitis. It may also be the origin of the neuropsychiatric symptoms that can occur after some systemic infections. 14
  15. 15. CONCLUSIONS Recent scientific evidence is leading to a greater understanding of the complexities and intricacies of chemical communication in the brain. The importance and relevance of both fast/precise and slow/summative types of communication have yet to be fully appreciated. Advancing knowledge is gradually elucidating the roles that volume transmission plays in supporting normal function. Also, this mode of chemical communication provides new avenues with great potential for intervening in neurodegenerative conditions, after acute trauma, and in the development of novel therapeutics for chronic psychiatric conditions that, to date , do not have satisfactory treatments. 15
  16. 16. BRAIN: THE ULTIMATE WONDERLAND KEEP EXPLORING STAY EVER SURPRISED THANK YOU 16

Search related