Synaptic Plasticity

The only way to modify the communication between two neurons is to enhance or reduce the response of the [blank_start]post[blank_end]synaptic neuron.

Habituation saves [blank_start]energy[blank_end].

Short-term changes are driven by [blank_start]passive[blank_end] processes, long-term changes are driven by [blank_start]active[blank_end] processes.

The gill-withdrawal reflex in aplysia can be sensitized (potentiated) when tail and mantle shelf are stimulated

Short term potentiation in aplysia An action potential arrives through the sensory neuron and [blank_start]Ca2+[blank_end] influx leads to transmitter release into the synaptic cleft. Neurotransmitters from the interneuron lead to the release of [blank_start]Protein kinase A[blank_end] (PKA) within the presynaptic sensory neuron. PKA does three things: (a) K+ channels are [blank_start]inhibited[blank_end] and the AP stays longer (b) Synaptic vesicles are [blank_start]phosphorelated[blank_end] (c) The [blank_start]exocytosis[blank_end] of the synaptic vesicles is sensitized. Additionally, [blank_start]calmodulin[blank_end] reacts on Ca2+ and amplifies the whole mehanism.

Long-term potentiation in aplysia (1) [blank_start]PKA[blank_end] activates genes in nucles (2) [blank_start]Ubiquitin hydrolase[blank_end] makes PKA more stable (3) [blank_start]New synaptic connections are grown[blank_end] The facilitating interneuon does not depolarize the sensory neuron! It only modulates!

The molecular learning processes in aplysia involve [blank_start]only presynaptic[blank_end] mechanisms.

In the hippocampus neurons from the dentate region [blank_start]induce[blank_end] LTP. This happens via the [blank_start]mossy fiber pathway[blank_end] (dentate region to CA3). Neurons from the other hemisphere [blank_start]do not induce[blank_end] LTP. Their signals travel via the [blank_start]commissural pathway[blank_end].

During LTP there is also a feedback signal to the presynaptic cell. One example is [blank_start]NO[blank_end], which [blank_start]diffuses[blank_end] to the presynaptic cell.

The mechanism for long-term potentiation

Early phase of long-term potentiation: During normal, low-frequency synaptic transmission Na+ and K+ flow only through [blank_start]AMPA[blank_end] receptors. During a high or repeated depolarization of the postsynaptic membrane the [blank_start]Mg2+[blank_end] blockade of the [blank_start]NMDA[blank_end] receptors is released and K+, Na+ and Ca2+ flow through these channels. This leads to an electric-independent [blank_start]Ca2+[blank_end] signal.

During the late phase of LTP

The discusses model of early and late LTP is holds for CA3 and CA1 neurons and therefore for the

The importance of NMDA receptors for LTP can be seen in a behavioral experiment with knockout-mice.

A receptor critically involved in LTP is [blank_start]NMDA[blank_end].

The early phase of LTP makes use of [blank_start]cGMP[blank_end]. It is [blank_start]short[blank_end]-lasting and [blank_start]does not require[blank_end] protein synthesis. The late phase of LTP makes use of [blank_start]cAMP[blank_end]. It is [blank_start]long[blank_end]-lasting and [blank_start]requires[blank_end] protein synthesis.

Since there are so many different neuronal phenotypes that all serve different purposes, the [blank_start]morphology[blank_end] of a neuron is very important when it comes to STP and LTP.

While the dendrites of neurons are [blank_start]relatively stable[blank_end], filopodia are [blank_start]dynamic[blank_end] and can extend and retract. After a contact to [blank_start]a neighbouring axon[blank_end], the filopodium [blank_start]becomes a dendritic spine[blank_end]. The process of filopodia growth is triggered by electrical activity and the activation of [blank_start]NMDA[blank_end] receptors.

Overexpression of [blank_start]SynCAM (synaptic cell adhesion molecule)[blank_end] in [blank_start]HEK (human embryonic kidney)[blank_end] cells leads to expression of synapses.

The more mature the neuron, the [blank_start]better[blank_end] the LTP. The more mature the neuron, the [blank_start]less dense[blank_end] are its protrusions (filopodia).

Molecules like SynCAM that initiate intracellular synaptogenesis programs are called [blank_start]extracellular recognition molecules[blank_end].

Developing neurons have [blank_start]low[blank_end] potential for synaptic plasticity because [blank_start]stable[blank_end] synapses are required for proper synapse function.

Attached to the postsynaptic membrane is [blank_start]PSD[blank_end] ([blank_start]postsynaptic density[blank_end]). It ensures receptors are in close proximity to presynaptic neurotransmitter release sites.

The postsynaptic region is a very rigid structure

CaMKII (a Ca-dependent protein kinase) sits [blank_start]directly behind[blank_end] the NMDA receptors.

On the postsynaptic site short-term plasticity can be achieved by bringing more receptors to the post-synaptic membrane. This is done with [blank_start]AMPA[blank_end] receptors.

Three models of the formation of new dendritic spines

[blank_start]NMDA[blank_end] receptor properties provide the biological correlate for Hebb's postulate. [blank_start]Presynaptic[blank_end] glutamate release depolarizes the postsynaptic neuron via [blank_start]AMPA[blank_end] receptors. After removal of the [blank_start]Mg2+[blank_end] block by depolarization glutamate causes [blank_start]Ca2+[blank_end] influx via NMDA receptors. Ca2+-dependent [blank_start]postsynaptic[blank_end] mechanisms lead then to the change in synaptic efficacy. Coincidence detector: [blank_start]NMDA receptors[blank_end] Coincidence signal: [blank_start]Ca2+ flux[blank_end]

Different relations between spike-timing and long term effects (LTP or LTD) are possible! A timing of +- [blank_start]5 ms[blank_end] can be critical.

A very important role in LTP play [blank_start]theta[blank_end]-rhythms. The [blank_start]formatio reticularis[blank_end] activates the [blank_start]septum[blank_end] with a rhythm of [blank_start]10-30[blank_end] Hz. The rhythm is received by [blank_start]granule cells[blank_end] and [blank_start]CA1[blank_end] neurons in the [blank_start]hippocampus[blank_end]. To induce LTP an action potential must reach a CA1 at the [blank_start]peak[blank_end] of the theta-oscillation.

The unidirection of pre- and postsynaptic cells exists [blank_start]only on the synaptic level[blank_end]. Neurons [blank_start]can[blank_end] (can or cannot) be pre- and postsynaptic to each other simultaneously.

A kind of backpropagation within the cells happens when an AP travels from the cell body back to the dendrites. This is called [blank_start]dendritic action potential[blank_end].

[blank_start]Single[blank_end] synaptic contacts can lead to LTP or LTD processes triggering multiple neuronal circuit processes.

The decision whether a signal is propagated forward through the axon or backward to the dendrites is made at the [blank_start]soma[blank_end].

In what respect are dendritic action potentials different to APs in the axon?

What are these different types of inputs called?

There can be different types of STDP even within one neuron, depending on the location, e.g. further down the axon or at the dendrites.

Triggering of backpropagating dendritic spikes is influenced by [blank_start]biochemical properties of dendrites[blank_end].

Active dendritic properties such as dendritic spikes are crucial for synaptic integration and plasticity.

Synapses far away from cell body are more sensitive for STDP.

Short-term habituation in aplysia's gill withdrawal reflex are due to [blank_start]reduced transmitter release[blank_end]. [blank_start]There are no[blank_end] postsynaptic changes in glutamate receptor density.

Short-term potentiation in aplysia Release of [blank_start]serotonin[blank_end] of the facilitating interneuron leads to activation of [blank_start]adenylyl cyclase[blank_end], the production of [blank_start]cAMP[blank_end] and release of inhibition on [blank_start]PKA[blank_end]. PKA [blank_start]blocks[blank_end] K+ channels which leads to a longer action potential. PKA also [blank_start]increases[blank_end] the exocytosis of neurotransmitters and [blank_start]opens[blank_end] further Ca2+ channels. An amplifying mechanism is provided by [blank_start]calmodulin[blank_end] which activates more adenylyl cyclase.

Persistent activity of PKA is modulated by [blank_start]ubiquitin hydrolase[blank_end] and leads to the growth of new [blank_start]synapses[blank_end].

NMDA receptors work as a coincidence detector in LTP. The two signals that must be present are: - [blank_start]depolarization[blank_end] of the postsynaptic cell - [blank_start]glutamate[blank_end] in the synaptic cleft

SynCAM is expressed in the [blank_start]dendritic[blank_end] cell. It is an extracellular recognition molecule, meaning that it [blank_start]sticks out of the membrane[blank_end].

In the early phase of LTP on the presynaptic site [blank_start]more[blank_end] neurotransmitters are released and on the postsynaptic site new [blank_start]AMPA[blank_end] receptors are brought to the membrane.

During the late phase of LTP new synapses are grown via [blank_start]CREB[blank_end]-mediated gene expression.