By improving the stability of field recordings in in vitro electrophysiology, it waspossible to investigate the molecular processes that determine the long-term changesin synaptic efficacy.
Fragile X Syndrome (FXS) due to the loss of FMRP is believed to be a disease of excess translation that ultimately leads to altered plasticity. Our central hypothesis is that loss of FMRP leads to the deregulation of synaptic actin and that this is a significant molecular endpoint that is causal to the behavioral deficits in Fragile X Syndrome. The rationale for this hypothesis is based on several lines of evidence:
The information transmitting end of the cone cell is known as the pedicle and of the rod cell as the spherule. Cone pedicles are large, conical, flat end-feet (8-10 µm diameter) of the cone axon that lie more or less side by side on the same plane at the outer edge of the outer plexiform layer (OPL)(Figs. 23a and b). The more numerous rod spherules, in contrast, are small round enlargements of the axon (3-5 µm diameter) or even extensions of the cell body. They lie packed between and above the cone pedicles (Fig. 23a and b). Both photoreceptor types’ synaptic endings are filled with synaptic vesicles. At their synapses to second-order neurons (bipolar and horizontal cells), both rod spherules and cone pedicles exhibit dense structures known as synaptic ribbons pointing to the postsynaptic invaginated processes (asterisks in Fig. 24). In the cone pedicle approximately 30 of these ribbons occur and are associated with 30 “triads” of invaginated processes (Ahnelt et al., 1990). In the rod spherule 2 ribbons are associated with 4 invaginated second-order neurites while the cone pedicle delivers information to over a hundred second-order neurons (Fig. 23b).
Thus it is also because our brainsis plastic - and because plasticity is competitive - that it is so hardto learn a new language and end the tyranny of the mother tongue."[In fact when a second language is learned it is normally processed ina brain area quite different to the linguistic area of the mothertongue.]
When Neuroscientists talk about plasticity of thebrain they are not talking about polymers, they are talking about theability of the brain to respond, adapt, and continually change i.e.
Classically, both the quantal theory and the vesicle theory predict that the amount of transmitter producing a miniature is determined presynaptically prior to release and that rapid changes in miniature amplitude reflect essentially postsynaptic alterations.
Psychosocial stress- or hypothyroidism-induced changes in synaptic plasticity generated a shift in the sliding threshold of modification ( θ m ) toward LTD.
In this study, we applied synaptic plasticity changes induced by either chronic psychosocial stress or hypothyroidism, and their restoration by chronic nicotine treatment, to the sliding threshold model.
If a presynaptic spike arrives before a postsynapticspike, the upregulation of the NMDA receptors in combination with the activitation 1up of the first second-messenger triggerssynaptic changes that lead to LTP.
In the dark a steady current flows into the open channels, carried mainly by Na ions, constituting a “dark current” that partially depolarizes the photoreceptor cell (Fig. 10). Thus, the depolarized photoreceptor releases neurotransmitter (the amino acid glutamate) from its synaptic terminals upon second-order neurons in the dark. On light stimulation the rhodopsin molecules are isomerized to the active form, the above cascade ensues, leading to closure of the cation channels of the photoreceptor membrane, stopping the dark current and causing the photoreceptor cell membrane to hyperpolarize and cease neurotransmitter release to second-order neurons (Fig. 10) (see Stryer, 1991; Yau, 1994, and Kawamura, 1995, and Fu (webvision) for reviews).
(2001b) suggest that down-regulation of the NMDA receptor is mediated by the intracellular calcium concentration that changes with eachpostsynaptic spike.
The deterioration of the brain that occurs during Alzheimer’s is due to the plaques from amyloid beta proteins clumping together. Amyloid beta is an indicator of Alzheimer’s disease, present within the brain prior to Alzheimer’s disease patients becoming symptomatic of the disease. Small clumps of this protein can block synapsing between neuronal cells.
The secondary messenger up, which finally leads to LTP, isactivated by postsynaptic spikes, but only if up-regulated NMDA channels areavailable.
Let us now consider the synaptic change caused by a single presynaptic spikeat j(f) 0 and a postsynaptic spike a i(f) = j(f) - .