Abstract
Broad issues associated with non-replicability have been described in experimental pharmacological and behavioral cognitive studies. Efforts to prevent biases that contribute to non-replicable scientific protocols and to improve experimental rigor for reproducibility are increasingly seen as a basic requirement for the integrity of scientific research. Synaptic plasticity, encompassing long-term potentiation (LTP), is believed to underlie mechanisms of learning and memory. The present study was undertaken in Long-Evans (LE) rats, a strain of rat commonly used in cognitive behavioral tests, to (1) compare three LTP tetanisation protocols, namely, the high-frequency stimulation (HFS), the theta-burst stimulation (TBS), and the paired-pulse facilitation (PPF) at the Schaffer collateral-CA1 stratum radiatum synapse and to (2) assess sensitivity to acute pharmacology. Results: (1) When compared to Sprague-Dawley (SD) rats, the HFS using a stimulus intensity of 50% of the maximum slope obtained from input/output (I/O) curves elicited lower and higher thresholds of synaptic plasticity responses in SD and LE rats, respectively. The 2-train TBS protocol significantly enhanced the LTP response in LE rats over the 5- and 10-train TBS protocols in both strains, and the 5 × TBS protocol inducing a subthreshold LTP response was used in subsequent pharmacological studies in LE rats. The PPF protocol, investigating the locus of the LTP response, showed no difference for the selected interstimulus intervals. (2) Scopolamine, a nonspecific muscarinic antagonist, had a subtle effect, whereas donepezil, an acetylcholinesterase inhibitor, significantly enhanced the LTP response, demonstrating the sensitivity of the TBS protocol to enhanced cholinergic tone. MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, significantly reduced LTP response, while memantine, another NMDA antagonist, had no effect on LTP response, likely associated with a weaker TBS protocol. PQ10, a phosphodiesterase-10 inhibitor, significantly enhanced the TBS-induced LTP response, but did not change the PPF response. Overall, the results confirm the strain-dependent differences in the form of synaptic plasticity, replicate earlier plasticity results, and report effective protocols that generate a relatively subthreshold margin of LTP induction and maintenance, which are suitable for pharmacology in the LE rat strain mainly used in cognitive studies.
Highlights
Cognitive function can be defined as cerebral activities and processes involved in acquiring new knowledge and understanding thoughts, experiences, and senses, encompassing attention, memory, perception, language comprehension, decision making and judgment, and executive control functions [1]
The present study evaluated the margin of plasticity response to three long-term potentiation (LTP) protocols (HFS, theta-burst stimulation (TBS), and paired-pulse facilitation (PPF)) at the SC-CA1 hippocampal circuit in anesthetized LE rats, which is a commonly used strain in behavioral cognitive tests
We have evaluated three LTP induction protocols in anesthetized LE rats: high-frequency stimulation (HFS), TBS, and PPF
Summary
Cognitive function can be defined as cerebral activities and processes involved in acquiring new knowledge and understanding thoughts, experiences, and senses, encompassing attention, memory, perception, language comprehension, decision making and judgment, and executive control functions [1]. These complex processes rely on the exchange of information between critical brain regions through synaptic transmission. Synaptic plasticity encompasses two main processes: long-term potentiation (LTP) and long-term depression (LTD) characterized as a persistent increase and decrease in synaptic strength, respectively.
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