Frequency-dependent changes in synaptic plasticity and brain-derived neurotrophic factor (BDNF) expression in the CA1 to perirhinal cortex projection

Abstract

The ability of a synapse to be modulated both positively and negatively may be considered as a plausible model for the formation of learning and memory. The CA1 to perirhinal cortex projection is one of the multiple hippocampal–neocortical projections considered to be crucially involved in memory consolidation. We and others have previously demonstrated the ability of this projection to undergo long-term potentiation (LTP), however it is currently unknown whether the CA1-perirhinal projection can also be modified negatively (i.e. demonstrate long-term depression (LTD)). Here we investigate whether the CA1 to perirhinal projection in vivo in the anaesthetised animal shows a frequency-dependent pattern of synaptic plasticity that is coupled with brain-derived neurotrophic factor (BDNF) expression. Five groups of animals were used and each group underwent one of five different stimulation protocols (1 Hz, 5 Hz, 10 Hz, 50 Hz or 100 Hz) followed by post-stimulation recordings at baseline stimulation intensity (0.05 Hz) for 1 h. Paired-pulse facilitation (PPF) recordings were taken both during baseline and 1 h post-stimulation across six inter-pulse intervals (IPIs). Following all experiments, tissue samples were taken from area CA1 and perirhinal cortex from both the unstimulated and stimulated hemispheres of each brain and analysed for BDNF. Results indicated that LTP was observed following 50 Hz and 100 Hz HFS but LTD was not observed following any low-frequency stimulation. Pre- and post-stimulation PPF recordings revealed no difference for any of the stimulation frequencies, suggesting that the plasticity observed may involve a post- rather than a presynaptic mechanism. Finally, changes in BDNF were positively correlated with stimulation frequency in the area CA1 but the same pattern was not observed in the perirhinal cortex. These findings suggest that the CA1 to perirhinal cortex projection is electrophysiologically excitatory in nature and that changes in BDNF levels in this projection may not be predictive of changes in synaptic plasticity.