Synaptic plasticity

Anlagen:

• Techniques in synaptic plasticity
• TECHNIQUES

Anmerkungen:

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

1. Induction

   Anlagen:

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

         Anmerkungen:

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

         Anmerkungen:

         • 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

         Anmerkungen:

         • 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

            Anmerkungen:

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

         Anmerkungen:

         • 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

            Anmerkungen:

            • 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

            Anmerkungen:

            • 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

            Anmerkungen:

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

            Anmerkungen:

            • 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

               Anmerkungen:

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

            Anmerkungen:

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

               Anmerkungen:

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

            Anmerkungen:

            • 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

            Anlagen:

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

      Anlagen:

      • Metaplasticity
2. Expression

   Anlagen:

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

         Anlagen:

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

   Anlagen:

   • Induction of LTP
   1. endogenous
      1. endocannabinoids

         Anlagen:

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

      Anlagen:

      • Metaplasticity
4. General
   1. Hebb's postulate

      Anmerkungen:

      • “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

      Anmerkungen:

      • ‘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

            Anmerkungen:

            • in rabbbits
            1. Extracellular recordings
               1. fEPSP

                  Anmerkungen:

                  • 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

               Anmerkungen:

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

         Anmerkungen:

         • 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

            Anmerkungen:

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

               Anmerkungen:

               • 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

            Anmerkungen:

            • 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

         Anmerkungen:

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

               Anmerkungen:

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

         Anmerkungen:

         • 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

               Anmerkungen:

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

         Anmerkungen:

         • 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

   Anlagen:

   • Synaptic plasticity at different brain regions
   1. HPC

      Anlagen:

      • 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)

Anmerkungen:

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

Anlagen:

• LTD
• mGluR-dependent LTD
• LTD

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

1. Memory and leanring
2. Stress

   Anmerkungen:

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

Anlagen:

• Developmental plasticity
• Critical periods and local circuits

1. structural changes

   Anlagen:

   • Structural plasticity

Anlagen:

• Short-term synaptic plasticity

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

   Anlagen:

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

      Anlagen:

      • Endocannabinoids in synaptic plasticity