UVM Theses and Dissertations
Format:
Print
Author:
Fuchs, Jason R.
Dept./Program:
Psychology
Year:
2013
Degree:
M.A.
Abstract:
Eyeblink classical conditioning (EBCC) is a well-studied form of classical conditioning that is used to study the underlying mechanisms of learning and memory. The learned response in EBCC is an eyeblink conditioned response (CR). Eyeblink conditioning relies on interactions between Purkinje cells (PCs) in cerebellar cortex and neurons in one of the deep cerebellar nuclei, the interpositus nucleus (lPN). In order for eyeblink CRs to emerge, the inhibition of PCs on the IPN must be lifted, to allow the conditioning stimulus to IPN connections to be strengthened. Basket cells (BC) are small, cortical, inhibitory interneurons whose axon terminals are proximally located near the PC axon hillock. Given the ideal location of BC axon terminals, these cells may be situated exert powerful control over PC output and thus, exert powerful control over acquisition of CRs. BC axon terminals express the highest concentration of the [alpha]-subunit ofthe voltage-gated K channel, Kv1.2 in the cerebellum.
Research has shown that blocking this channel increases the frequency of inhibitory postsynaptic currents (lPSCs) in Purkinje cells. Additionally, regulation of this channel has been linked to the neuropeptide secretin. Previous research shows that PCs express and release secretin, surface Kv1.2 in BC terminals is reduced by secretin and secretin increases IPSCs in PCs, which is blocked by GABAA antagonists. Based on these observations, we examined the role that Kv1.2 and secretin have on EBCC.
In Experiment 1, rats were infused with secretin or vehicle into lobulus simplex of the cerebellar cortex immediately prior to the first 3 days of EBCC. Infusions of secretin facilitated EBCC. In Experiment 2, rats were infused with either the secretin receptor antagonist, 5-27 secretin, or vehicle immediately prior to the first 3 days of conditioning. Rats that received 5-27 secretin showed slower learning than the vehicle-treated rats. In Experiment 3, rats received infusions of either tityustoxin-Ka. (TSTX), a highly potent Kvl. 2 blocker, or vehicle into lobulus simplex immediately prior to each of 6 conditioning sessions. The rats that received infusions of TSTX displayed enhanced conditioning. In Experiment 4, rats were infused with a smaller volume of TSTX or vehicle into lobulus simplex of the cerebellar cortex immediately prior to the first 2 conditioning sessions.
In this experiment, there was no significant facilitation in the percentage of eRs, but rats that received infusions of TSTX showed greater CR amplitude than the vehicle treated rats on the first day of EBCC. The results demonstrate support for secretin and Kv1.2 acting to modulate PC output and EBCC. Our working model is that secretin released by PCs modulates EBCC by reducing surface levels of Kv1.2 at BC terminals, thereby increasing inhibition of PCs.
Research has shown that blocking this channel increases the frequency of inhibitory postsynaptic currents (lPSCs) in Purkinje cells. Additionally, regulation of this channel has been linked to the neuropeptide secretin. Previous research shows that PCs express and release secretin, surface Kv1.2 in BC terminals is reduced by secretin and secretin increases IPSCs in PCs, which is blocked by GABAA antagonists. Based on these observations, we examined the role that Kv1.2 and secretin have on EBCC.
In Experiment 1, rats were infused with secretin or vehicle into lobulus simplex of the cerebellar cortex immediately prior to the first 3 days of EBCC. Infusions of secretin facilitated EBCC. In Experiment 2, rats were infused with either the secretin receptor antagonist, 5-27 secretin, or vehicle immediately prior to the first 3 days of conditioning. Rats that received 5-27 secretin showed slower learning than the vehicle-treated rats. In Experiment 3, rats received infusions of either tityustoxin-Ka. (TSTX), a highly potent Kvl. 2 blocker, or vehicle into lobulus simplex immediately prior to each of 6 conditioning sessions. The rats that received infusions of TSTX displayed enhanced conditioning. In Experiment 4, rats were infused with a smaller volume of TSTX or vehicle into lobulus simplex of the cerebellar cortex immediately prior to the first 2 conditioning sessions.
In this experiment, there was no significant facilitation in the percentage of eRs, but rats that received infusions of TSTX showed greater CR amplitude than the vehicle treated rats on the first day of EBCC. The results demonstrate support for secretin and Kv1.2 acting to modulate PC output and EBCC. Our working model is that secretin released by PCs modulates EBCC by reducing surface levels of Kv1.2 at BC terminals, thereby increasing inhibition of PCs.