An investigation into Cocaine and amphetamine regulated transcript (CART) peptide in the rat cerebellum

Cocaine and Amphetamine Regulated Transcript (CART) peptide is a putative neuropeptide, which has been implicated in a variety of physiological processes including feeding, reward and reinforcement and locomotion. . However, CART peptide receptors have not yet been identified and CART peptide's mechanism of action still remains unclear. Using immunohistochemistry, I have confirmed the presence of CART peptide in fibres in the vestibular cerebellum (lobes IX and X and the paraflocculus) and have shown that the CART peptide has a banded distribution. Co-localisation with Vesicle Glutamate Transporter 2 (vGluT2) demonstrated CART peptide expression at climbing fibre-Purkinje cell synapses. Thus CART peptide may act as a neurotransmitter. Application of CART peptide (fragment amino acids 55-102), significantly increased the firing rate of vestibular Purkinje cells, an effect that persisted when synaptic inputs were blocked. CART peptide appeared to directly depolarise the membrane potential of Purkinje cells, and this may underlie the observed increase in firing rate. CART peptide did not modulate excitatory or inhibitory inputs onto Purkinje cells, and did not appear to have a role in synaptic plasticity. I have investigated what controls the firing rate and pattern of firing of Purkinje cells ill vitro. The major factor is the activity of inhibitory interneurones whereas excitatory inputs have little effect. I have identified 7 different firing patterns and have shown that blocking synaptic inhibition not only changes the firing rate, but also the firing pattern. I have also demonstrated that the AMPA receptor antagonist, 6-cyano-7- nitroquinoxaline-2,3-dione(CNQX) has a direct excitatory effect on Purkinje cells, increasing the firing rate and depolarising the membrane potential.EThOS - Electronic Theses Online ServiceGBUnited Kingdo