AbstractCholinergic modulation of the medial prefrontal cortex (mPFC) is important in attentional and mnemonic processes. These functions are mediated by excitatory pyramidal neurons and inhibitory interneurons within the mPFC. The largest class of neocortical interneurons, parvalbumin-expressing interneurons (PV+), create recurrent connections with excitatory pyramidal neurons within the mPFC. Little is known about how the strength of the connection between PV+ and pyramidal neurons within the deeper layers of the mPFC is modulated during sustained activity or how this activity is influenced by the neurotransmitter acetylcholine.
Using whole-cell paired recordings between PV+ interneurons and pyramidal neurons within layer 5/6 of the mPFC, the short-term dynamics of these connections were investigated over a wide range of frequencies (5 – 200Hz). Model selection identified the most parsimonious short-term plasticity models to capture the dynamics between these cells. While the excitatory synapse is best described with a simple short-term depression model, the inhibitory synapse is best explained by a model which includes heterogeneous vesicle pools with different release probabilities.
Activation of acetylcholine receptors with carbachol reduced the strength of the connection between pyramidal and PV+ neurons. Furthermore, carbachol reduced the short-term depression of inhibitory transmission at frequencies above 20Hz. The mechanisms underlying this shift in short-term plasticity were investigated using short-term plasticity models. Computational modelling indicated that the change in short-term depression is mediated by reduction in release probability and slower vesicle replenishment.
These findings show that the underlying mechanisms of short-term plasticity in excitatory and inhibitory transmission are mediated by different processes and that the connection between PV+ and pyramidal neurons is subject to cholinergic modulation.
|Date of Award||25 Jun 2019|
|Supervisor||Zafar I Bashir (Supervisor) & Conor J Houghton (Supervisor)|