The Effects of Cholinergic Loss in the Septodentate Pathway on Long-Term Potentiation Induction in the Perforant Path of Sprague-Dawley Rats: A Case Study
Long-term potentiation (LTP) is considered a neurophysiological correlate of learning and memory characterized by strengthening of connections between neurons and increased synaptic efficiency. LTP has been demonstrated to occur in the hippocampus, which has an established role in learning and memory. The dentate gyrus (DG) of the hippocampus receives innervation from the medial septum/nucleus of the diagonal band of Broca through the septodentate pathway (SD). In addition, the entorhinal cortex (EC) innervates the DG via the perforant path (PP). The role of the SD, particularly the cholinergic division, is considered essential in memory function. Glutamatergic and GABAergic neurons are also located in the SD, thus to examine the role of cholinergic SD neurons we performed extracellular electrophysiological recordings in rats that had received an injection of a selective cholinergic neurotoxin, 192-IgG saporin, in the septum of male, Sprague-Dawley rats. After a three-week recovery period recordings were obtained from the DG following paired-pulse, heterosynaptic stimulation of the septum (preliminary, conditioning pulse) and EC (test pulse). Population spikes in the DG in response to PP stimulation were measured at stimulation intensities of 25%, 50%, 90%, and 100% as determined by an input-output curve. The impact of the septal stimulation on the DG response after PP stimulation was explored from 40 min before and up to 130 minutes after LTP was induced by a high-frequency-stimulation tetanization protocol. Four different interpulse intervals of 30, 60, 100, and 500 ms were used to characterize the effect of septal stimulation on the PP response. The cholinergic neuronal marker acetylcholinesterase (AChE) was labeled in DG to determine the extent of loss caused by IgG-saporin. The degree of AChE labeling in the DG (quantified using optical densitometry) indicated there was one successful case, 1758, of cholinergic SD neuronal deafferentation of the DG. Interestingly, electrophysiological analysis indicated a depression of the PP after a high-frequency tetanization protocol in this one case. This indicates that the cholinergic neurons of the SD pathway are involved in LTP induction ability within this neuronal system.