Blockade of GABAA receptors in the interpositus nucleus modulates expression of conditioned excitation but not conditioned inhibition of the eyeblink response

Abstract

The cerebellum and related brainstem structures are essential for excitatory eyeblink conditioning. Recent evidence indicates that the cerebellar interpositus and lateral pontine nuclei may also play critical roles in conditioned inhibition (CI) of the eyeblink response. The current study examined the role of GABAergic inhibition of the interpositus nucleus in retention of CI. Male Long-Evans rats were implanted with a cannula positioned just above or in the anterior interpositus nucleus before training. The rats were trained with two different tones and a light as conditioned stimuli, and a periorbital shock as the unconditioned stimulus. CI training consisted of four phases: 1) excitatory conditioning (8 kHz tone paired with shock); 2) feature-negative discrimination (2 kHz tone paired with shock or 2 kHz tone concurrent with light); 3) summation test (8 kHz tone or 8 kHz tone concurrent with light); and 4) retardation test (light paired with shock). After reaching a criterion level of performance on the feature-negative discrimination (40% discrimination), 0.5 μl picrotoxin (a GABA A receptor antagonist) was infused at one of four concentrations, each concentration infused during separate test sessions. Picrotoxin transiently impaired conditioned responses during trials with the excitatory stimulus (tone) in a dose-dependent manner, but did not significantly impact responding to the inhibitory compound stimulus (tone-light). The results suggest that expression of conditioned inhibition of the eyeblink conditioned response does not require GABAergic inhibition of neurons in the anterior interpositus nucleus.

Amygdala, deep cerebellar nuclei and red nucleus contribute to delay eyeblink conditioning in C57BL /6 mice

“…Furthermore, there are conflicting results on eyeblink conditioning performed in DCNlesioned mice (Chen et al, 1999;Koekkoek et al, 2003;Wada et al, 2007). We observed incomplete loss of CRs in mice with DCN inactivation by the GABA A agonist muscimol (MSC) (Sakamoto & Endo, 2008), and this is different from what has been found for rabbit (Krupa et al, 1993;Krupa & Thompson, 1997;Bao et al, 2002, Aksenov, et al, 2004 and rat (Nolan et al, 2002;Freeman et al, 2005) eyeblink conditioning.…”

Perirhinal cortex lesions impair feature-negative discrimination☆

“…On each of the ten days of phase 1 training, all rats received a 100-trial session of featurenegative discrimination training, which consisted of 50 T 1 + and 50 LT 1 − trials. This procedure has been used in previous studies to establish conditioned inhibition (Freeman & Nicholson, 1999;Nolan, Nicholson, & Freeman, 2002;Freeman et al, 2005). The compound stimulus was presented simultaneously, where onsets and offsets for T 1 and L occurred together.…”

Differential Effects of Cerebellar Inactivation on Eyeblink Conditioned Excitation and Inhibition

“…The conditioned inhibition procedure consisted of 50 paired trials with the tone CS used in phase 1 followed by the US and 50 trials with the tone CS and a light CS presented simultaneously without the US. The conditioned inhibition procedure was designed to establish the light CS as an inhibitory stimulus (Freeman and Nicholson, 1999;Nicholson and Freeman, 2002;Nolan et al, 2002). During phase 3, conditioned inhibition training continued in the absence of infusions.…”

“…Variants of the standard classical conditioning procedure can be used to produce inhibition of CRs by establishing a second CS as a predictor that the US will be omitted. A commonly used method for establishing inhibitory learning is to present standard CS-US conditioning trials mixed with trials in which the original CS (CSA) is presented with a second CS (CSX) simultaneously, and the compound stimulus is not paired with the US (Pavlov, 1927;Freeman and Nicholson, 1999;Nicholson and Freeman, 2002;Nolan et al, 2002). As a result of this discrimination training, CSX will inhibit the CR that would otherwise be elicited by CSA.…”

“…Eyeblink conditioning has been used as a model system for examining the neural mechanisms of standard (excitatory) classical conditioning and, to a lesser extent, inhibitory conditioning (Mis, 1977;Berthier and Moore, 1980;Moore et al, 1980;Yeo et al,1983;Blazis and Moore, 1991;Freeman and Nicholson, 1999;Nicholson and Freeman, 2002;Nolan et al, 2002;Christian and Thompson, 2003). Excitatory conditioning requires the intermediate cerebellum including the interpositus nucleus, anterior lobe, hemispheric lobule VI, and perhaps other cortical regions (Christian and Thompson, 2003).…”