Epigenetic Involvement in Heterosynaptic (Tagged) LTP Following Beta-Adrenergic Receptor Activation in the Mouse Hippocampus

• Author / Creator

  Brandwein, Nathan

• Synapses experience long-lasting plastic changes following neuromodulatory action in the brain. One natural modulator is noradrenaline (NA). Beta-adrenergic receptor (b-AR) activation by noradrenaline enhances memory formation and long-term potentiation (LTP), a form of synaptic plasticity characterized by an activity-dependent increase in synaptic strength. Since LTP is believed to be a cellular correlate of learning and memory, understanding the mechanisms by which synapses undergo LTP is necessary for grasping how the brain encodes information. In the mammalian hippocampus, a brain structure responsible for new memory formation, LTP can be observed at multiple synaptic sites after strong stimulation of a single synaptic pathway. This phenomenon, referred to as synaptic tagging, may permit distinct synaptic pathways to associate information from separate, convergent synaptic inputs. Previous research has revealed that synaptic tagging requires protein synthesis, and that both transcription and epigenetic modifications are necessary for eliciting LTP at a single homosynaptic site (Maity et al., 2016). However, it is unclear whether transfer of LTP to a secondary heterosynaptic site involves b-ARs signalling to the nucleus. The present thesis uses electrophysiological protocols to show that pharmacological inhibition of b-ARs, mRNA synthesis or histone acetyltransferase prevents heterosynaptic plasticity in mouse CA1 hippocampal neurons. Thus, heterosynaptic “tagged” LTP must recruit nuclear signalling by engaging transcription and histone acetylation. Future research should investigate how these intracellular mechanisms modulate memory consolidation in combination with in vivo behavioural models. This will allow for a more complete characterization of how mRNA and proteins enable the endurance of long-term memories.

• Subjects / Keywords

  • memory
  • long-term potentiation
  • hippocampus
  • epigenetics
  • noradrenaline

• Graduation date

  Spring 2019

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-23dc-xt26

• License

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