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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.


Related in: MedlinePlus

(A,B) Electromyography (EMG) recorded from eye muscles (orbicularis oculi) of the left upper eyelid during trace eyeblink conditioning. Each line represents EMG activity from an individual trial (1–100, with Trial 1 represented at the bottom of each figure and Trial 100 represented at the top of each figure) from Session 7 of 500-ms trace eyeblink classical conditioning. Total trial length was 1,350 ms. Lines are drawn to approximate the onset of the conditioned stimulus (CS) and unconditioned stimulus (US). There were 249 ms in the pre-CS period before CS onset. CS onset is marked, and then there were 500 ms between CS onset and US onset (marked). There were 601 ms in the post-US period. A response was scored if it exceeded the peak of pre-CS activity by 1.5 units. Performance is shown for a wild-type control mouse (A) and an α7 knockout (KO) mouse (B) that were representative of their respective groups in terms of CR production levels. For the wild-type control mouse shown here (A), 95 of the 100 trials were usable for analyses; the remaining 5 trials were excluded due to excessive pre CS EMG activity. During paired CS–US trials this subject (A) displayed conditioned responses (CRs) on 88% of the trials. Short latency alpha (or “startle”) responses (0–60 ms after CS onset) occurred in 58% of the paired CS–US trials. For the α7 KO subject (B), 93 of the 100 trials were usable for analysis. During paired CS–US trials there were 63% CRs and 24% alpha responses.
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Figure 2: (A,B) Electromyography (EMG) recorded from eye muscles (orbicularis oculi) of the left upper eyelid during trace eyeblink conditioning. Each line represents EMG activity from an individual trial (1–100, with Trial 1 represented at the bottom of each figure and Trial 100 represented at the top of each figure) from Session 7 of 500-ms trace eyeblink classical conditioning. Total trial length was 1,350 ms. Lines are drawn to approximate the onset of the conditioned stimulus (CS) and unconditioned stimulus (US). There were 249 ms in the pre-CS period before CS onset. CS onset is marked, and then there were 500 ms between CS onset and US onset (marked). There were 601 ms in the post-US period. A response was scored if it exceeded the peak of pre-CS activity by 1.5 units. Performance is shown for a wild-type control mouse (A) and an α7 knockout (KO) mouse (B) that were representative of their respective groups in terms of CR production levels. For the wild-type control mouse shown here (A), 95 of the 100 trials were usable for analyses; the remaining 5 trials were excluded due to excessive pre CS EMG activity. During paired CS–US trials this subject (A) displayed conditioned responses (CRs) on 88% of the trials. Short latency alpha (or “startle”) responses (0–60 ms after CS onset) occurred in 58% of the paired CS–US trials. For the α7 KO subject (B), 93 of the 100 trials were usable for analysis. During paired CS–US trials there were 63% CRs and 24% alpha responses.

Mentions: Mice were run for 10 days in 500 ms delay or 500 ms trace eyeblink classical conditioning (500 ms ISI between CS and US onset for both tasks) with each day consisting of one session of 90 paired CS–US and 10 CS alone trials. Each training session was controlled by a program written in C++ language (Chen and Steinmetz, 1998). The intertrial interval was random, ranging from 15 to 30-s at 1-s intervals. Mice were trained in groups of four. Each session lasted approximately 1 h and mice were allowed to move about freely within the beaker during testing. The ventilation fan generated a 70-dB background noise. Each daily session (10 sessions of acquisition total) consisted of 100 trials (presented in blocks of 10). Each 10-trial block consisted of nine paired trials and one CS-alone test trial. Delay eyeblink conditioning trials included a 600-ms 85-db white noise CS. Five hundred milliseconds after CS onset, a 100-ms 0.5 mA stimulation US was delivered, and this coterminated with the CS. Trace eyeblink conditioning paired trials included a 250-ms white noise CS also followed 500 ms after its onset (and 250 ms after its offset) by a 100-ms 0.5 mA stimulation US. The 250 ms period between CS offset and US onset represented a stimulus-free “trace” interval [see Figure 2 for sample EMG recordings from a wild-type control (Figure 2A) and an α7 KO (Figure 2B) trained in trace conditioning].


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)

(A,B) Electromyography (EMG) recorded from eye muscles (orbicularis oculi) of the left upper eyelid during trace eyeblink conditioning. Each line represents EMG activity from an individual trial (1–100, with Trial 1 represented at the bottom of each figure and Trial 100 represented at the top of each figure) from Session 7 of 500-ms trace eyeblink classical conditioning. Total trial length was 1,350 ms. Lines are drawn to approximate the onset of the conditioned stimulus (CS) and unconditioned stimulus (US). There were 249 ms in the pre-CS period before CS onset. CS onset is marked, and then there were 500 ms between CS onset and US onset (marked). There were 601 ms in the post-US period. A response was scored if it exceeded the peak of pre-CS activity by 1.5 units. Performance is shown for a wild-type control mouse (A) and an α7 knockout (KO) mouse (B) that were representative of their respective groups in terms of CR production levels. For the wild-type control mouse shown here (A), 95 of the 100 trials were usable for analyses; the remaining 5 trials were excluded due to excessive pre CS EMG activity. During paired CS–US trials this subject (A) displayed conditioned responses (CRs) on 88% of the trials. Short latency alpha (or “startle”) responses (0–60 ms after CS onset) occurred in 58% of the paired CS–US trials. For the α7 KO subject (B), 93 of the 100 trials were usable for analysis. During paired CS–US trials there were 63% CRs and 24% alpha responses.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2958052&req=5

Figure 2: (A,B) Electromyography (EMG) recorded from eye muscles (orbicularis oculi) of the left upper eyelid during trace eyeblink conditioning. Each line represents EMG activity from an individual trial (1–100, with Trial 1 represented at the bottom of each figure and Trial 100 represented at the top of each figure) from Session 7 of 500-ms trace eyeblink classical conditioning. Total trial length was 1,350 ms. Lines are drawn to approximate the onset of the conditioned stimulus (CS) and unconditioned stimulus (US). There were 249 ms in the pre-CS period before CS onset. CS onset is marked, and then there were 500 ms between CS onset and US onset (marked). There were 601 ms in the post-US period. A response was scored if it exceeded the peak of pre-CS activity by 1.5 units. Performance is shown for a wild-type control mouse (A) and an α7 knockout (KO) mouse (B) that were representative of their respective groups in terms of CR production levels. For the wild-type control mouse shown here (A), 95 of the 100 trials were usable for analyses; the remaining 5 trials were excluded due to excessive pre CS EMG activity. During paired CS–US trials this subject (A) displayed conditioned responses (CRs) on 88% of the trials. Short latency alpha (or “startle”) responses (0–60 ms after CS onset) occurred in 58% of the paired CS–US trials. For the α7 KO subject (B), 93 of the 100 trials were usable for analysis. During paired CS–US trials there were 63% CRs and 24% alpha responses.
Mentions: Mice were run for 10 days in 500 ms delay or 500 ms trace eyeblink classical conditioning (500 ms ISI between CS and US onset for both tasks) with each day consisting of one session of 90 paired CS–US and 10 CS alone trials. Each training session was controlled by a program written in C++ language (Chen and Steinmetz, 1998). The intertrial interval was random, ranging from 15 to 30-s at 1-s intervals. Mice were trained in groups of four. Each session lasted approximately 1 h and mice were allowed to move about freely within the beaker during testing. The ventilation fan generated a 70-dB background noise. Each daily session (10 sessions of acquisition total) consisted of 100 trials (presented in blocks of 10). Each 10-trial block consisted of nine paired trials and one CS-alone test trial. Delay eyeblink conditioning trials included a 600-ms 85-db white noise CS. Five hundred milliseconds after CS onset, a 100-ms 0.5 mA stimulation US was delivered, and this coterminated with the CS. Trace eyeblink conditioning paired trials included a 250-ms white noise CS also followed 500 ms after its onset (and 250 ms after its offset) by a 100-ms 0.5 mA stimulation US. The 250 ms period between CS offset and US onset represented a stimulus-free “trace” interval [see Figure 2 for sample EMG recordings from a wild-type control (Figure 2A) and an α7 KO (Figure 2B) trained in trace conditioning].

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.


Related in: MedlinePlus