Classical eyeblink conditioning using electrical stimulation of caudal mPFC as conditioned stimulus is dependent on cerebellar interpositus nucleus in guinea pigs

Abstract

Aim: To determine whether electrical stimulation of caudal medial prefrontal cortex (mPFC) as conditioned stimulus (CS) paired with airpuff unconditioned stimulus (US) was sufficient for establishing eyeblink conditioning in guinea pigs, and whether it was dependent on cerebellar interpositus nucleus. Methods: Thirty adult guinea pigs were divided into 3 conditioned groups, and trained on the delay eyeblink conditioning, short-trace eyeblink conditioning, and long-trace eyeblink conditioning paradigms, respectively, in which electrical stimulation of the right caudal mPFC was used as CS and paired with corneal airpuff US. A pseudo conditioned group of another 10 adult guinea pigs was given unpaired caudal mPFC electrical stimulation and the US. Muscimol (1 µg in 1 µL saline) and saline (1 µL) were infused into the cerebellar interpositus nucleus of the animals through the infusion cannula on d 11 and 12, respectively. Results: The 3 eyeblink conditioning paradigms have been successfully established in guinea pigs. The animals acquired the delay and short-trace conditioned responses more rapidly than long-trace conditioned responses. Muscimol infusion into the cerebellar interpositus nucleus markedly impaired the expression of the 3 eyeblink conditioned responses. Conclusion: Electrical stimulation of caudal mPFC is effective CS for establishing eyeblink conditioning in guinea pigs, and it is dependent on the cerebellar interpositus nucleus.

Optogenetic stimulation of mPFC pyramidal neurons as a conditioned stimulus supports associative learning in rats

“…Interestingly, although the above results suggest that optogenetic activation of the right caudal mPFC pyramidal neurons as a CS was sufficient for establishing DEC, the CR% after acquisition was relatively low (~40%) compared with results typically obtained with either a tone CS (~90%) 0 or electrical stimulation of caudal mPFC as a CS (~90%) 7 . This phenomenon prompted us to perform a set of experiments to explore the possible reason.…”

“…Although optical activation of the right caudal mPFC pyramidal neurons as a CS was sufficient to support DEC, the acquisition CR% was relatively low (~40%) compared with results obtained with a electrical stimulation of caudal mPFC as a CS (~90%) 7 . One possibility is that optical stimulation activated a small number of mPFC pyramidal neurons, while electrical stimulation did not.…”

“…However, the c-Fos results showed that large numbers of mPFC pyramidal neurons were activated by optical stimulation ( Supplementary Fig. S2a–d ) and increasing the power density of light failed to produce similar levels of CR% compared with a electrical CS in our previous study 7 ( Supplementary Fig. S4a ).…”

Pretrial functional connectivity differentiates behavioral outcomes during trace eyeblink conditioning in the rabbit

“…When right whisker vibration is repeatedly paired with an airpuff to the right cornea in trace eyeblink conditioning (tEBC), the left SI and right IPN are important for acquisition and memory retrieval (Woodruff-Pak et al 1985;Galvez et al 2007;Green and Arenos 2007;Plakke et al 2007;Pakaprot et al 2009;Hu et al 2010Hu et al , 2012Wu et al 2012). If either are lesioned prior to the start of training, the tEBC task will not be acquired.…”

“…The hippocampus (Solomon et al 1986;Moyer et al 1990;Kim et al 1995;Weiss et al 1999), medial prefrontal cortex (Kronforst-Collins and Disterhoft 1998;Weible et al 2000;McLaughlin et al 2002;Takehara et al 2003), and somatosensory cortex (Galvez et al 2007) are essential in whiskersignaled trace conditioning. In addition, the neural pathway of the CS, US, and conditioned blink all incorporate the cerebellar interpositus nucleus (IPN) (Woodruff-Pak et al 1985;Green and Arenos 2007;Plakke et al 2007;Pakaprot et al 2009;Hu et al 2010Hu et al , 2012Wu et al 2012) and it is in this region where information about the CS and US both converge (McCormick et al 1982;Clark et al 1984;Yeo et al 1985;Lavond and Steinmetz 1989;Krupa et al 1993Krupa et al , 1996Thompson 1995, 1997;Thompson 2003, 2005).…”