Synaptic plasticity

Adjunto:

• Techniques in synaptic plasticity
• TECHNIQUES

Nota:

• Increase in synaptic efficacy. Cells that fire together, wire together

1. Induction

   Adjunto:

   • Induction of LTP
   1. Properties
      1. 1. Long lasting

         Nota:

         • It can last from a number of hours to days 
         1. Bliss and Gardner-Medwin (1973)
      2. 2.Cooperativity

         Nota:

         • weak stimulation of many afferents produces larger excitatory post-synaptic potential (EPSP). When action potentials propagate simultaneously at more than two different synapses, on a pre-synaptic neuron, they summate at a post-synaptic neuron to cause a Ca2+ influx, which initiates LTP 
         1. Douglas and Goddard, 1975
         2. Collingeifge et al, 1983
      3. 3. Associatively

         Nota:

         • by varying the intensity of the stimulations on two different pathways (i.e. one is strong and one is weak) you can initiate LTP, even if the strong stimulation alone wouldn’t initiate LTP. In this way, the plasticity associates not only the synapse that provided strong stimulation, but also the one provided the weak stimulation 
         1. McNaughton et al., 1978

            Nota:

            • a weak input could be potentiated if its activation coincided with a tetanus to another input
      4. 4. Input-specific

         Nota:

         • CA1 region in the hippocampus, it was demonstrated that LTP can be generated only at one synaptic set. It doesn’t “spread” to other synapses that were not associated with the induction of depolarisation in the post-synaptic neuron. Also, it means that the storage capacity of an individual neuron can significantly increase following LTP 
         1. Bliss et al., 1973

            Nota:

            • Analysis of input output curves suggested that only the synaptic inputs that had actually been tetanized were potentiated, a phenomenon called “input specificity”
         3. Andersen et al. 1977

            Nota:

            • LTP of the fEPSP was induced in the tetanized pathway, whereas the response evoked in the second, untetanized pathway remained at baseline levels
      5. Other
         1. Reversible
         2. Saturated

            Nota:

            • - i.e. there is a point where the connection will no longer increase
         3. Paired stimulation

            Nota:

            • Paired stimulation of the presynaptic neuron and the postsynaptic terminal– This was demonstrated by the California Aplysia in a classical conditioning in the gill-withdrawal reflex>> as long as the pre-synaptic and post-synaptic depolarisation (And is sufficient to induce action potentials) is directly correlated, LTP will be induced (Murphy & Glanzman, 1997)   
            1. Murphy & Glanzman, 1997

               Nota:

               • in the california aplysia
         4. Doesn't change PPR

            Nota:

            • a change in PPR indicates a presynaptic, short-term mechanism
         5. EPSP-spike (E-S) potentiation
            1. Andersen et al., 1980

               Nota:

               • an increase in the coupling between the synaptic response and the population spike
   2. Molecular mechanisms
      1. Ca2+
      2. Receptors
         1. NMDAR

            Nota:

            • conditions required for the induction of LTP are identical to the conditions required for the activation of the NMDA receptor, and that the cellular event that triggers the induction of LTP is the influx of Ca2 through the activated NMDA receptor

            Adjunto:

            • General synaptic platicity
         2. metabotropic glutamate receptors
         3. GABA receptors
   3. Protocols
      1. theta
      2. tetanic
      3. paired
         1. spike timing-dependent
   4. metaplasticity

      Adjunto:

      • Metaplasticity
2. Expression

   Adjunto:

   • Expression of LTP
   1. Presynaptic
      1. STP
      2. Early LTP
   2. Postsynaptic
      1. Structural changes

         Adjunto:

         • Structural plasticity
      2. ELTP
      3. LLTP
3. Modulation

   Adjunto:

   • Induction of LTP
   1. endogenous
      1. endocannabinoids

         Adjunto:

         • Endocannabinoids in synaptic plasticity
      2. Corticosteriords, NA
   2. Glial
   3. metaplasticity

      Adjunto:

      • Metaplasticity
4. General
   1. Hebb's postulate

      Nota:

      • “When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased” Hebb, 1949
   2. Hebbian plasticity

      Nota:

      • ‘Hebbian’ plasticity now refers to the need for both preand post-synaptic activity to occur simultaneously for long-term synaptic modification to occur
   3. Discovery
      1. Bliss and Lomo (1973)
         1. DG in-vivo

            Nota:

            • in rabbbits
            1. Extracellular recordings
               1. fEPSP

                  Nota:

                  • potentiation of the field EPSP (fEPSP) was accompanied by an increase in the amplitude and a decrease in the latency of the population spike
            2. perforant path
            3. tetanic stimulation

               Nota:

               • Tetanic stimulation of 100 Hz for 3 to 4 seconds or, more usually, 15 Hz for 10 to 20 seconds
      2. Andersen, 1960

         Nota:

         • Working with anesthetized rabbits, Andersen had earlier observed that field potentials evoked by stimulation at frequencies of 1 Hz or less were stable, whereas the response to successive stimuli grew steadily larger when the stimulus frequency was stepped up to 5 to 10 Hz
         1. anaesthetized rabbits
      3. Bliss and Gardner-Medwin (1973)
         1. tetanus-induced potentiation

            Nota:

            • could persist for many days in the unanesthetized rabbit with chronically implanted electrodes
            1. long-term property

               Nota:

               • Potentiation was not seen with low-intensity tetanization but required a stimulation strength that exceeded a threshold approximately equal to that required to activate a population spike
      4. Block LTP
         1. Douglas et al., 1982

            Nota:

            • by delivering a coincident high-frequency train to the commissural input to the dentate gyrus commissural stimulation suppressed the firing of granule cells, this last result suggested that the “locus of control” for induction was postsynaptic
   4. Phases
      1. Early LTP

         Nota:

         • produces an increase in probability in transmitter release without structural changes Over an hour
         1. protein kinase-dependent
            1. protein kinase inhibitors

               Nota:

               • duration of potentiation to an hour
         2. minutes-hours
      2. Late LTP

         Nota:

         • leads in increase in postsynaptic receptors, structural changes such as increases in dendritic connections  Hours-days
         1. protein synthesis- dependent
            1. protein synthesis / trascription inhibitors

               Nota:

               • potentiated response in area CA1 of hippocampal slices returns to baseline within 5 to 6 hours
         2. hours-days-months
      3. Metaplasticity

         Nota:

         • The history of synaptic activity is an additional variable that influences the synaptic state
      4. short-term
         1. seconds-minutes
   5. Drugs
      1. DDG/ AVP
         1. NMDA receptor anta
5. NMDAR dependent
6. In animals
   1. macaque monkeys
      1. Urban et al., 1996
   2. Humans
      1. Beck et al., 2000; reviewed by Cooke and Bliss, 2006
   3. vertebrate species, including rats, guinea pigs, mice, and chicks
      1. Margrie et al., 1998
7. In the brain

   Adjunto:

   • Synaptic plasticity at different brain regions
   1. HPC

      Adjunto:

      • General synaptic platicity
      1. perforant path to granule cells
      2. mossy fibers to CA3 cells
      3. Schaffer collaterals to CA1 cells
      4. perforant path projections to area:
         1. CA3- Do et al., 2002
         2. CA1- Colbert and Levy, 1993
      5. CA1-subiculum
         1. O’Mara et al., 2000
      6. in some but not all excitatory connections onto hippocampal interneurons
         1. Lamsa et al., 2005
      7. CA1 neurons on a class of macroglia-like cells (Ge et al., 2006)
   2. cerebellum (Crépel and Jaillard, 1991)
   3. amygdala (Chapman et al., 1990)
   4. sensory cortex (Artola and Singer, 1987)
   5. prefrontal cortex (Laroche et al., 1990)
   6. nucleus accumbens (Kombian and Malenka, 1994)

Nota:

• A reverse form of hebbian plasticity- reduction in synaptic efficacy, or weakening of synaptic connections

Adjunto:

• LTD
• mGluR-dependent LTD
• LTD

1. NMDAR-dependent
2. NMDAR-dependent
3. NMDAR-independent

1. Memory and leanring
2. Stress

   Nota:

   • see stress and synaptic plasticity essay
3. Disease
   1. Parkinsons
   2. Schizophrenia
   3. Alzheimers
   4. Addication

Adjunto:

• Developmental plasticity
• Critical periods and local circuits

1. structural changes

   Adjunto:

   • Structural plasticity

Adjunto:

• Short-term synaptic plasticity

1. NMDAR-independent
2. facilitation
3. depression
4. PTP/ agumentation
5. Role of Ca
6. Role of receptors

   Adjunto:

   • Receptor mediated STP
   1. GABA
   2. Endocannabinoid and DSI/DSE

      Adjunto:

      • Endocannabinoids in synaptic plasticity