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Trace eyeblink conditioning is impaired in α7 but not in β2 nicotinic acetylcholine receptor knockout mice.

Brown KL, Comalli DM, De Biasi M, Woodruff-Pak DS - Front Behav Neurosci (2010)

Bottom Line: The two most common forms of eyeblink classical conditioning - the delay and trace paradigms - differentially engage forebrain areas densely-populated with nAChRs.Elevated conditioned response levels in delay-conditioned β2 KOs corresponded to elevated levels of alpha responding in this group.The prominent distribution of α7 nAChRs in the hippocampus and other forebrain regions may account for these genotype-specific acquisition effects in this hippocampus-dependent trace paradigm.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Program and Department of Psychology, Temple University Philadelphia, PA, USA.

ABSTRACT
Nicotinic acetylcholine receptors (nAChRs) are essentially involved in learning and memory. A neurobiologically and behaviorally well-characterized measure of learning and memory, eyeblink classical conditioning, is sensitive to disruptions in acetylcholine neurotransmission. The two most common forms of eyeblink classical conditioning - the delay and trace paradigms - differentially engage forebrain areas densely-populated with nAChRs. The present study used genetically modified mice to investigate the effects of selective nAChR subunit deletion on delay and trace eyeblink classical conditioning. α7 and β2 nAChR subunit knockout (KO) mice and their wild-type littermates were trained for 10 daily sessions in a 500-ms delay or 500-ms trace eyeblink conditioning task, matched for the interstimulus interval between conditioned stimulus and unconditioned stimulus onset. Impairments in conditioned responding were found in α7 KO mice trained in trace - but not delay - eyeblink conditioning. Relative to littermate controls, β2 KO mice were unimpaired in the trace task but displayed higher levels of conditioned responding in delay eyeblink conditioning. Elevated conditioned response levels in delay-conditioned β2 KOs corresponded to elevated levels of alpha responding in this group. These findings suggest that α7 nAChRs play a role in normal acquisition of 500 ms trace eyeblink classical conditioning in mice. The prominent distribution of α7 nAChRs in the hippocampus and other forebrain regions may account for these genotype-specific acquisition effects in this hippocampus-dependent trace paradigm.

No MeSH data available.


Percentage of alpha responding [responses occurring within the first 60 ms of conditioned stimulus – CS – onset] over 10 sessions in the same subjects and same sessions depicted in Figures 3 and 4: Twenty-six wild-type control mice (15 in delay and 11 trained in trace), 20 α7 KO mice (10 in delay and 10 trained in trace), and 24 β2 KO mice (12 in delay and 12 trained in trace). Delay eyeblink conditioning is depicted on the left side and trace eyeblink conditioning is shown on the right. Comparisons between wild-type controls and α7 KOs are shown on the top (A,B) panels, while comparisons between wild-type controls and β2 KOs are shown across the bottom (C,D) panels. The error bars indicate standard error of the mean.
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Figure 5: Percentage of alpha responding [responses occurring within the first 60 ms of conditioned stimulus – CS – onset] over 10 sessions in the same subjects and same sessions depicted in Figures 3 and 4: Twenty-six wild-type control mice (15 in delay and 11 trained in trace), 20 α7 KO mice (10 in delay and 10 trained in trace), and 24 β2 KO mice (12 in delay and 12 trained in trace). Delay eyeblink conditioning is depicted on the left side and trace eyeblink conditioning is shown on the right. Comparisons between wild-type controls and α7 KOs are shown on the top (A,B) panels, while comparisons between wild-type controls and β2 KOs are shown across the bottom (C,D) panels. The error bars indicate standard error of the mean.

Mentions: Levels of alpha responding (responses that exceeded threshold within the first 60 ms of CS onset) differed across some groups. Separate 2 (genotype) × 10 (sessions) ANOVAs revealed significant effects of genotype [F(1, 25) = 5.861, p < 0.024] and Genotype × Sessions [F(9. 225) = 2.488, p < 0.011] for the comparison between β2 KOs and wild-type controls trained in the delay eyeblink classical conditioning paradigm (the main effect of session failed to reach significance in this comparison – p > 0.1). These significant effects involving the factor of genotype were driven by significantly elevated levels of alpha (or “startle”) responding – particularly early in training – in β2 KOs relative to wild-types trained in delay conditioning. For the three remaining comparisons across genotype – α7 KOs versus wild-types in delay and in trace conditioning; β2 KOs versus wild-types in trace conditioning – no significant effects involving the factor of genotype were observed for the startle percentage measure (all p values >0.1). A significant main effect of sessions was observed across each of these three comparisons (all p values <0.007) (see Figure 5).


Trace eyeblink conditioning is impaired in α7 but not in β2 nicotinic acetylcholine receptor knockout mice.

Brown KL, Comalli DM, De Biasi M, Woodruff-Pak DS - Front Behav Neurosci (2010)

Percentage of alpha responding [responses occurring within the first 60 ms of conditioned stimulus – CS – onset] over 10 sessions in the same subjects and same sessions depicted in Figures 3 and 4: Twenty-six wild-type control mice (15 in delay and 11 trained in trace), 20 α7 KO mice (10 in delay and 10 trained in trace), and 24 β2 KO mice (12 in delay and 12 trained in trace). Delay eyeblink conditioning is depicted on the left side and trace eyeblink conditioning is shown on the right. Comparisons between wild-type controls and α7 KOs are shown on the top (A,B) panels, while comparisons between wild-type controls and β2 KOs are shown across the bottom (C,D) panels. The error bars indicate standard error of the mean.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2958052&req=5

Figure 5: Percentage of alpha responding [responses occurring within the first 60 ms of conditioned stimulus – CS – onset] over 10 sessions in the same subjects and same sessions depicted in Figures 3 and 4: Twenty-six wild-type control mice (15 in delay and 11 trained in trace), 20 α7 KO mice (10 in delay and 10 trained in trace), and 24 β2 KO mice (12 in delay and 12 trained in trace). Delay eyeblink conditioning is depicted on the left side and trace eyeblink conditioning is shown on the right. Comparisons between wild-type controls and α7 KOs are shown on the top (A,B) panels, while comparisons between wild-type controls and β2 KOs are shown across the bottom (C,D) panels. The error bars indicate standard error of the mean.
Mentions: Levels of alpha responding (responses that exceeded threshold within the first 60 ms of CS onset) differed across some groups. Separate 2 (genotype) × 10 (sessions) ANOVAs revealed significant effects of genotype [F(1, 25) = 5.861, p < 0.024] and Genotype × Sessions [F(9. 225) = 2.488, p < 0.011] for the comparison between β2 KOs and wild-type controls trained in the delay eyeblink classical conditioning paradigm (the main effect of session failed to reach significance in this comparison – p > 0.1). These significant effects involving the factor of genotype were driven by significantly elevated levels of alpha (or “startle”) responding – particularly early in training – in β2 KOs relative to wild-types trained in delay conditioning. For the three remaining comparisons across genotype – α7 KOs versus wild-types in delay and in trace conditioning; β2 KOs versus wild-types in trace conditioning – no significant effects involving the factor of genotype were observed for the startle percentage measure (all p values >0.1). A significant main effect of sessions was observed across each of these three comparisons (all p values <0.007) (see Figure 5).

Bottom Line: The two most common forms of eyeblink classical conditioning - the delay and trace paradigms - differentially engage forebrain areas densely-populated with nAChRs.Elevated conditioned response levels in delay-conditioned β2 KOs corresponded to elevated levels of alpha responding in this group.The prominent distribution of α7 nAChRs in the hippocampus and other forebrain regions may account for these genotype-specific acquisition effects in this hippocampus-dependent trace paradigm.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Program and Department of Psychology, Temple University Philadelphia, PA, USA.

ABSTRACT
Nicotinic acetylcholine receptors (nAChRs) are essentially involved in learning and memory. A neurobiologically and behaviorally well-characterized measure of learning and memory, eyeblink classical conditioning, is sensitive to disruptions in acetylcholine neurotransmission. The two most common forms of eyeblink classical conditioning - the delay and trace paradigms - differentially engage forebrain areas densely-populated with nAChRs. The present study used genetically modified mice to investigate the effects of selective nAChR subunit deletion on delay and trace eyeblink classical conditioning. α7 and β2 nAChR subunit knockout (KO) mice and their wild-type littermates were trained for 10 daily sessions in a 500-ms delay or 500-ms trace eyeblink conditioning task, matched for the interstimulus interval between conditioned stimulus and unconditioned stimulus onset. Impairments in conditioned responding were found in α7 KO mice trained in trace - but not delay - eyeblink conditioning. Relative to littermate controls, β2 KO mice were unimpaired in the trace task but displayed higher levels of conditioned responding in delay eyeblink conditioning. Elevated conditioned response levels in delay-conditioned β2 KOs corresponded to elevated levels of alpha responding in this group. These findings suggest that α7 nAChRs play a role in normal acquisition of 500 ms trace eyeblink classical conditioning in mice. The prominent distribution of α7 nAChRs in the hippocampus and other forebrain regions may account for these genotype-specific acquisition effects in this hippocampus-dependent trace paradigm.

No MeSH data available.