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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.


Illustration of the delay (A) and trace (B) eyeblink classical conditioning tasks used in the present study. The tasks were matched for the 500 ms interval between conditioned stimulus (CS) onset and unconditioned stimulus (US) onset. In delay conditioning, the CS precedes, overlaps, and coterminates with the 100 ms US. In trace conditioning, the CS precedes the US, but a 250-ms stimulus-free (trace) interval is imposed between the offset of the CS and the onset of the US.
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Figure 1: Illustration of the delay (A) and trace (B) eyeblink classical conditioning tasks used in the present study. The tasks were matched for the 500 ms interval between conditioned stimulus (CS) onset and unconditioned stimulus (US) onset. In delay conditioning, the CS precedes, overlaps, and coterminates with the 100 ms US. In trace conditioning, the CS precedes the US, but a 250-ms stimulus-free (trace) interval is imposed between the offset of the CS and the onset of the US.

Mentions: To explore further the role of nAChR subunit function in learning and memory, we assessed the performance of α7 and β2 nAChR KO mice in delay and trace eyeblink conditioning tasks matched for the 500 ms interstimulus interval (ISI) between CS and US onset (see Figure 1 for an illustration of our delay and trace tasks). Previous work in our laboratory with the 750 ms ISI in New Zealand white rabbits (Woodruff-Pak et al., 2007) and the 500 ms ISI in C57BL/6 mice (Spath and Woodruff-Pak, 2004) indicated that when ISIs are matched in the trace and delay paradigms, acquisition in trace is slower and reaches a lower asymptote. ISI-matched delay and trace eyeblink conditioning tasks differentially engage forebrain circuitry associated with higher-order learning and memory paradigms (Moyer et al., 1990; Ivkovich and Stanton, 2001; Green and Arenos, 2007). The 500-ms trace eyeblink conditioning paradigm with a 250-ms trace interval is hippocampus-dependent in mice (Tseng et al., 2004). Because of the prominent distribution and known functional properties of α7 nAChRs in the hippocampus (Séguéla et al., 1993; Cincotta et al., 2008; De Biasi and Salas, 2008), we predicted greater impairments in the hippocampus-sensitive trace task in α7 nAChR KO mice. Additionally, due to the greater importance of hippocampal integrity for acquisition of trace relative to delay eyeblink conditioning, conditioning impairments in α7 nAChR KO mice were expected to be greater in trace than those in delay-conditioned α7 or β2 nAChR KO mice.


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)

Illustration of the delay (A) and trace (B) eyeblink classical conditioning tasks used in the present study. The tasks were matched for the 500 ms interval between conditioned stimulus (CS) onset and unconditioned stimulus (US) onset. In delay conditioning, the CS precedes, overlaps, and coterminates with the 100 ms US. In trace conditioning, the CS precedes the US, but a 250-ms stimulus-free (trace) interval is imposed between the offset of the CS and the onset of the US.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Illustration of the delay (A) and trace (B) eyeblink classical conditioning tasks used in the present study. The tasks were matched for the 500 ms interval between conditioned stimulus (CS) onset and unconditioned stimulus (US) onset. In delay conditioning, the CS precedes, overlaps, and coterminates with the 100 ms US. In trace conditioning, the CS precedes the US, but a 250-ms stimulus-free (trace) interval is imposed between the offset of the CS and the onset of the US.
Mentions: To explore further the role of nAChR subunit function in learning and memory, we assessed the performance of α7 and β2 nAChR KO mice in delay and trace eyeblink conditioning tasks matched for the 500 ms interstimulus interval (ISI) between CS and US onset (see Figure 1 for an illustration of our delay and trace tasks). Previous work in our laboratory with the 750 ms ISI in New Zealand white rabbits (Woodruff-Pak et al., 2007) and the 500 ms ISI in C57BL/6 mice (Spath and Woodruff-Pak, 2004) indicated that when ISIs are matched in the trace and delay paradigms, acquisition in trace is slower and reaches a lower asymptote. ISI-matched delay and trace eyeblink conditioning tasks differentially engage forebrain circuitry associated with higher-order learning and memory paradigms (Moyer et al., 1990; Ivkovich and Stanton, 2001; Green and Arenos, 2007). The 500-ms trace eyeblink conditioning paradigm with a 250-ms trace interval is hippocampus-dependent in mice (Tseng et al., 2004). Because of the prominent distribution and known functional properties of α7 nAChRs in the hippocampus (Séguéla et al., 1993; Cincotta et al., 2008; De Biasi and Salas, 2008), we predicted greater impairments in the hippocampus-sensitive trace task in α7 nAChR KO mice. Additionally, due to the greater importance of hippocampal integrity for acquisition of trace relative to delay eyeblink conditioning, conditioning impairments in α7 nAChR KO mice were expected to be greater in trace than those in delay-conditioned α7 or β2 nAChR KO mice.

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.