Lec11_02 Long Term Potentiation

Long Term Potentiation (LTP)

  • Long term potentiation is synonymous with learning in neurological terms.

  • Defined as semi-permanent structural and connectivity changes among neurons due to experience.

  • Increases likelihood of activity along repeatedly used neural circuits.

Role of Glutamate in Learning

  • Glutamate is a key neurotransmitter involved in primary learning circuits, such as those in the hippocampus and basal ganglia.

  • Important in the formation of Hebbian synapses.

  • Has multiple receptor sites that need to be differentiated:

    • AMPA Receptors: Ionotropic; when glutamate binds, it opens ion channels allowing sodium and calcium to enter, thereby exciting the postsynaptic cell.

    • NMDA Receptors: Metabotropic; contain a magnesium ion blocking the channel's opening, preventing ion entry until released through enough stimulation of the circuit.

Mechanism of Action

  • AMPA Receptor Activation:

    • Glutamate binds and immediately opens up an excitatory ion channel.

    • Sodium and calcium ions enter the postsynaptic cell, leading to cell excitation.

  • NMDA Receptor Activation:

    • Initially blocked by magnesium, NMDA receptors allow ion entry after repetitive stimulation of AMPA receptors.

    • Frequent use leads to magnesium ejection, transforming NMDA receptors into ion channels similar to AMPA, facilitating heightened neuronal activity.

Dendritic Changes in Long Term Potentiation

  • With increased activity and experience, the postsynaptic cell can undergo structural changes:

    • Dendritic Branching: Enhanced surface area enables more receptor sites to be built, increasing capacity to receive glutamate.

    • Example: Proficiency at tasks increases dendritic branches in relevant brain areas (e.g., texting with thumbs).

Feedback Mechanisms during Development

  • During fetal development, postsynaptic cells can release neurotrophins, providing positive feedback to presynaptic cells to enhance neurotransmitter release.

  • This feedback mechanism is disrupted after birth in most neural circuits, where neurotransmitters are typically only released from presynaptic cells.

Exception: Retrograde Messengers

  • Certain memory circuits allow for retrograde signaling, where postsynaptic cells release chemicals (e.g., nitric oxide) providing feedback to presynaptic cells.

  • This retrograde signaling increases the probability of neurotransmitter release, enhancing communication and contributing to long term potentiation.