Young and older good learners have higher levels of brain nicotinic receptor binding

Woodruff-Pak, Diana S.; Lehr, Melissa A.; Li, Jianguo; Liu‐Chen, Lee‐Yuan

doi:10.1016/j.neurobiolaging.2008.09.002

Cited by 12 publications

(9 citation statements)

References 49 publications

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“…Performance variability among groups in our study does not appear to result from simple sensory or motor differences, given no differences in baseline acoustic physiology or initial escape latencies. A recent preliminary report suggests an anatomical correlate to our result, in that "good learners" of a classical conditioning task have higher levels of nAChRs ([ 3 H]epibatidine binding) in hippocampus and temporal-parietal cortex than "poor learners" (Woodruff-Pak, Lehr, Li, and Chen, 2007). Although nAChR binding levels do not always reflect function (due to, for example, receptor internalization, inactivation or desensitization), higher levels of cortical nAChRs could underlie our results in "good" performers.…”

Section: Discussionsupporting

confidence: 69%

Nicotinic modulation of tone-evoked responses in auditory cortex reflects the strength of prior auditory learning

Liang

Poytress

Weinberger

et al. 2008

Neurobiology of Learning and Memory

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Nicotinic acetylcholine receptors (nAChRs) contribute to sensory-cognitive function, as demonstrated by evidence that nAChR activation enhances, and nAChR blockade impairs, neural processing of sensory stimuli and sensory-cognitive behavior. To better understand the relationship between nAChR function and behavior, here we compare the strength of nAChR-mediated physiology in individual animals to their prior auditory behavioral performance. Adult rats were trained on an auditory-cued, active avoidance task over 4 days and classified as "good," "intermediate" or "poor" performers based on their initial rate of learning and eventual level of performance. Animals were then anesthetized, and tone-evoked local field potentials (LFPs) recorded in layer 4 of auditory cortex (ACx) before and after a test dose of nicotine (0.7mg/kg, s.c.) or saline. In "good" performers, nicotine enhanced LFP amplitude and decreased response threshold to characteristic frequency (CF) stimuli, yet had opposite effects (decreased amplitude, increased threshold) on responses to spectrally distant stimuli; i.e., cortical receptive fields became more selective for CF stimuli. In contrast, nicotine had little effect on LFP amplitude in "intermediate" or "poor" performing animals. Nicotine did, however, reduce LFP onset latency in all three groups, indicating that all received an effective dose of the drug. Our findings suggest that nicotinic regulation of cortical receptive fields may be a distinguishing feature of the best-performing animals, and may facilitate sensory-related learning by enhancing receptive field selectivity.

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Section: Discussionsupporting

confidence: 69%

Nicotinic modulation of tone-evoked responses in auditory cortex reflects the strength of prior auditory learning

Liang

Poytress

Weinberger

et al. 2008

Neurobiology of Learning and Memory

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“…In conclusion, our data add to previous findings suggesting that the VTA-hippocampus dopaminergic loop is a final common pathway for both top-down and bottom-up influences on late memory processing and indicates, as proposed formerly, that modulation of a7-nAChR may represent an important target for treatment of the increased forgetting observed in normal aging, mild cognitive impairment, and AD patients (Woodruff-Pak et al 2010;Kawamata and Shimohama 2011;Wallace and Porter 2011).…”

supporting

confidence: 87%

Nicotine modulates the long-lasting storage of fear memory

et al. 2013

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Late post-training activation of the ventral tegmental area (VTA) -hippocampus dopaminergic loop controls the entry of information into long-term memory (LTM). Nicotinic acetylcholine receptors (nAChR) modulate VTA function, but their involvement in LTM storage is unknown. Using pharmacological and behavioral tools, we found that a7-nAChR-mediated cholinergic interactions between the pedunculopontine tegmental nucleus and the medial prefrontal cortex modulate the duration of fear-motivated memories, maybe by regulating the activation state of VTA-hippocampus dopamine connections.Evidence suggests that nicotinic acetylcholine receptor (nAChR) agonists ameliorate the cognitive decline associated with schizophrenia and Alzheimer's disease (AD) progression (Barrantes et al. 2010;AhnAllen et al. 2012). Long-term memory (LTM) storage requires activation of the ventral tegmental area (VTA)-hippocampus dopaminergic loop (Lisman and Grace 2005) and synthesis of brain-derived neurotrophic factor (BDNF; Bekinschtein et al. 2007). Indeed, we have previously shown that the VTA-hippocampus loop is specifically active late after learning and, through a process involving the D1/D5 dopamine receptordependent increase of BDNF expression in the CA1 region of the dorsal hippocampus, determines LTM duration (Rossato et al. 2009). Therefore, since nicotine modulates VTA function (Wooltorton et al. 2003) and cholinergic inputs to the VTA have excitatory influence on mesolimbic dopamine neurons (Good and Lupica 2009;Yang et al. 2009;Zhao-Shea et al. 2011), contributing to signal behaviorally relevant events as well as the rewarding properties of stimuli Chen et al. 2006;Ikemoto 2007;Besson et al. 2012), we investigated the involvement of nAChRs on fear memory persistence. To that end, we utilized the step-down inhibitory avoidance (IA) learning task and 3-mo-old male Wistar rats. Animals were maintained under a 12-h light/dark cycle at 22˚C with ad libitum access to food and water. One week before training, rats were bilaterally implanted under deep anesthesia with 22-gauge guides aimed to the CA1 region of the dorsal hippocampus, the VTA, the medial prefrontal cortex (mPFC), the pedunculopontine tegmental nucleus (PPTg), and/or the laterodorsal tegmental nucleus (LDTg) in accordance with coordinates taken from the atlas of Paxinos and Watson 1986 (CA1: AP 24.2/LL + 3.0/DV 23.0; VTA: AP 24.8/LL + 1.0/ DV 29.0; mPFC: AP +3.2/LL + 0.8/DV 24.0; PPTg: AP 28.0/LL + 2.0/DV 28.0; LDTg: AP 29.1/LL + 0.7/ DV 28.0). IA training was carried out in a 50-cm × 25-cm × 25-cm Plexiglas box with a 5-cm-high, 8-cm-wide, and 25-cm-long wood platform on the left end of a series of bronze bars making the floor of the box. During training, the animals were placed on the platform facing the left rear corner of the box. When they stepped down to the grid, they received a 0.4 mA (weak training) or a 0.8 mA (strong training) scrambled footshock during 2 sec and were immediately withdrawn from the training box. LTM was assessed 2 d or 14 d later. Latency to step...

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“…Finally, the fact that the vast majority of relationships between nAChR binding and task performance were observed with α4β2* binding suggests that α4β2* nAChRs may play a more prominent role than α7 nAChRs in modulating cost benefit decision making. Indeed, in brain the α4β2* nAChR subtype is associated with release of dopamine and norepinephrine (both of which strongly modulate cost benefit decision making, Pattij and Vanderschuren, 2008) in most brain regions and predominates in density and distribution (Picciotto et al, 1998; Perry et al, 2002; Granon et al, 2003; Woodruff-Pak et al, 2008; Le Foll et al, 2009), whereas the α7 nAChR subtype comprises only about 10% of all nAChRs (Young et al, 2004; Keller et al, 2005; Curzon et al, 2006; Hoyle et al, 2006; see Figures 2 and 3). …”

Section: Discussionmentioning

confidence: 99%

α4β2∗ and α7 nicotinic acetylcholine receptor binding predicts choice preference in two cost benefit decision-making tasks

et al. 2013

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Nicotinic receptors have been linked to a wide range of cognitive and behavioral functions, but surprisingly little is known about their involvement in cost benefit decision making. The goal of these experiments was to determine how nicotinic acetylcholine receptor (nAChR) expression is related to two forms of cost benefit decision making. Male Long Evans rats were tested in probability and delay discounting tasks, which required discrete trial choices between a small reward and a large reward associated with varying probabilities of omission and varying delays to reward delivery, respectively. Following testing, radioligand binding to α4β2* and α7 nAChR subtypes in brain regions implicated in cost benefit decision making was examined. Significant linear relationships were observed between choice of the large delayed reward in the delay discounting task and α4β2* receptor binding in both dorsal and ventral hippocampus. Additionally, trends were found suggesting that choice of the large costly reward in both discounting tasks was inversely related to α4β2* receptor binding in the medial prefrontal cortex and nucleus accumbens shell. Similar, trends suggested that choice of the large delayed reward in the delay discounting task was inversely related to α4β2* receptor binding in the orbitofrontal cortex, nucleus accumbens core, and basolateral amygdala, as well as to α7 receptor binding in basolateral amygdala. These data suggest that nAChRs (particularly α4β2*) play both unique and common roles in decisions that require consideration of different types of reward costs.

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Young and older good learners have higher levels of brain nicotinic receptor binding

Cited by 12 publications

References 49 publications

Nicotinic modulation of tone-evoked responses in auditory cortex reflects the strength of prior auditory learning

Nicotinic modulation of tone-evoked responses in auditory cortex reflects the strength of prior auditory learning

Nicotine modulates the long-lasting storage of fear memory

α4β2∗ and α7 nicotinic acetylcholine receptor binding predicts choice preference in two cost benefit decision-making tasks

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