α7 Nicotinic acetylcholine receptors and temporal memory: Synergistic effects of combining prenatal choline and nicotine on reinforcement-induced resetting of an interval clock

Abstract

We previously showed that prenatal choline supplementation could increase the precision of timing and temporal memory and facilitate simultaneous temporal processing in mature and aged rats. In the present study, we investigated the ability of adult rats to selectively control the reinforcement-induced resetting of an internal clock as a function of prenatal drug treatments designed to affect the ␣7 nicotinic acetylcholine receptor (␣7 nAChR). Male Sprague-Dawley rats were exposed to prenatal choline (CHO), nicotine (NIC), methyllycaconitine (MLA), choline + nicotine (CHO + NIC), choline + nicotine + methyllycaconitine (CHO + NIC + MLA), or a control treatment (CON). Beginning at 4-mo-of-age, rats were trained on a peak-interval timing procedure in which food was available at 10-, 30-, and 90-sec criterion durations. At steady-state performance there were no differences in timing accuracy, precision, or resetting among the CON, MLA, and CHO + NIC + MLA treatments. It was observed that the CHO and NIC treatments produced a small, but significant increase in timing precision, but no change in accuracy or resetting. In contrast, the CHO + NIC prenatal treatment produced a dramatic increase in timing precision and selective control of the resetting mechanism with no change in overall timing accuracy. The synergistic effect of combining prenatal CHO and NIC treatments suggests an organizational change in ␣7 nAChR function that is dependent upon a combination of selective and nonselective nAChR stimulation during early development.

Prenatal choline supplementation increases sensitivity to time by reducing non-scalar sources of variance in adult temporal processing

“…In the mammalian brain, α7-nAChRs constitute one of the predominant nAChR subtypes and nicotine application to the ventral tegmental area, paired with postsynaptic stimulation, contributes to a form of long-term potentiation, an effect attributed to presynaptic α7-nAChRs on glutamatergic afferents (Jones and Wonnacott, 2004;Mansvelder and McGehee, 2000;Rousseau et al, 2005;Song et al, 2005). Of relevancy to the present study is the observation that prenatal choline supplementation increases the sensitivity of adult rats to the clock-speed enhancing effect of nicotine (Meck and Williams, 1997a), thus suggesting the possibility that prenatal choline supplementation can alter α7-nAChR function in adulthood (e.g., Cheng et al, 2006;Fayuk and Yakel, 2004;Gueseva et al, 2006;Morley et al, 1977;Stevens et al, 2007).…”

“…This prenatal choline-induced enhancement of temporal control is due, in part, to a reduced level of contamination by impulsive responses related to reinforcement probability and the delay to reward signaled by the onset of a conditioned stimulus that also serves to initiate the timing of the interval (see Cheng, 1992;Cheng et al, 2006Cheng et al, , 2007aChurch et al, 1991;Fantino et al, 1979). The observation that the "impulsive" responses of CON rats diminished as a function of lowered reinforcement probability and had less of an impact on the timing of longer intervals is consistent with the results reported for the PI procedure by and is in agreement with the finding that the initiation of responding in probe trials following a reinforced trial in the PI procedure is less sensitive to time than responding in probe trials preceded by another probe trial for shorter durations (e.g., 15 s) than for longer durations (e.g., 30 and 60 s) as reported by Church et al (1994).…”

“…This enhancement can be related to an increase in rats' sensitivity to the inhibitory effects of a signaled delay to reinforcement and the associated resetting of an internal clock by the delivery of reinforcement (Matell and Meck 1999;Cheng et al 2006). The question remains as to whether the increased temporal sensitivity exhibited by adult rats given prenatal choline supplementation differentially affects variance in clock, memory, or response thresholds (e.g., Buhusi, 2003;Cheng, 1992;Church 1984, 1992;Church et al 1991).…”

Circadian modulation of interval timing in mice

“…Striatal medium spiny neurons detect the coincident activity of specific beat patterns of cortical oscillations (Matell and Meck, 2004;Meck, 2006). Current evidence suggests that the pacemaker or internal clock which mediates the perception of short durations is sensitive to temperature, attention, emotions, drug and diet manipulations (e.g., Wearden and Penton-Voak, 1995;Cheng et al, 2006;Droit-Volet and Meck, 2007), all of which can be modulated by circadian rhythms. Although the suprachiasmatic nuclei appear to be unnecessary for interval timing (Lewis et al, 2003), time of day effects have been observed for the timing of auditory and visual signals in the seconds-to-minutes range (Aschoff, 1985;Chandrashekaran et al, 1991;Pati and Gupta, 1994;Meck, 1991).…”

Prenatal choline availability alters the context sensitivity of Pavlovian conditioning in adult rats

“…We know, for instance, that the adult offspring of pregnant rats supplemented with 4.5 times the amount of choline in the standard laboratory diet display improved memory capacity and precision on the radial-arm maze (e.g., Meck et al 1988Meck et al , 1989Williams 1997b, 1999;Tees 1999a), Morris water maze (e.g., Tees 1999b; Tees and Mohammadi 1999;Yang et al 2000;Brandner 2002), as well as facilitation of sustained attention and interval timing (e.g., Meck and Williams 1997a,c;Mohler et al 2001;Cheng et al 2006Cheng et al , 2008aCheng and Meck 2007) compared with offspring of dams fed a standard diet. Choline deficiency during the same developmental time frame, embryonic days (ED) 12-17, results in impaired performance on some, but not all, of these behavioral measures (e.g., Williams 1999, 2003).…”