Late-term moderate prenatal alcohol exposure impairs tactile, but not spatial, discrimination in a T-maze continuous performance task in juvenile rats

Abstract

Existing maze apparatuses used in rodents often exclusively assess spatial discriminability as a means to evaluate learning impairments. Spatial learning in such paradigms is reportedly spared by moderate prenatal alcohol exposure in rats, suggesting that spatial reinforcement alone is insufficient to delineate executive dysfunction, which consistently manifests in humans prenatally-exposed to alcohol. To address this, we designed a single-session continuous performance task in the T-maze apparatus that requires rats to discriminate within and between simultaneously-presented spatial (left or right) and tactile (sandpaper or smooth) stimuli for food reinforcement across four sequential discrimination stages: simple discrimination, intradimensional reversal 1, extradimensional shift, and intradimensional reversal 2. This design incorporates elements of working memory, attention, and goal-seeking behavior which collectively contribute to the executive function construct. Here, we found that rats prenatally-exposed to alcohol performed worse in both the tactile intradimensional reversal and extradimensional shift; alternatively, rats prenatally-exposed to alcohol acquired the extradimensional shift faster when shifting from the tactile to spatial dimension. In line with previous work, moderate prenatal alcohol exposure spared specifically spatial discrimination in this paradigm. However, when tactile stimuli were mapped into the spatial dimension, rats prenatally-exposed to alcohol required more trials to discriminate between the dimensions. We demonstrate that tactile stimuli can be operantly employed in a continuous performance T-maze task to detect discriminatory learning impairments in rats exposed to moderate prenatal alcohol. The current paradigm may be useful for assessing features of executive dysfunction in rodent models of fetal alcohol spectrum disorders.

Keywords: Executive function; Learning; Prenatal alcohol exposure; T-maze; Working memory.

Figure 1.. Experimental timeline.

Six (n = 6) gestating dams arrived at postnatal day 81 (PND81) and were at gestational day 6 (GD6) of their pregnancies. Dams were handled between GD7–13. Between GD14–20, dams received 2g/kg ethanol or isocaloric maltodextrin solution twice per day at 1000 and 1400hours. At PND21, offspring were individually housed. Offspring were singly-house and handled between PND22–27. Offspring were habituated to the T-maze for 7d between PND28–34. Offspring performed the sequential discrimination task between PND35–38. Figure artwork created with BioRender.com.

Figure 2.. Habituation procedure.

A) On habituation day 1, rats were placed directly in the center of the decision arms with the start arm blocked; rats were given 300 seconds to explore the sandpaper and smooth floors. B) Rats in the control (CTRL; n = 31) condition spent more time in the smooth floor arm compared to the sandpaper floor arm (B = 95.19, p <.001); rats with prenatal alcohol exposure (PAE; n = 30) spent an equivalent amount of time in the smooth and sandpaper floor arms. C) On habituation day 2, the sandpaper floor insert was removed and rats were placed in the start box to proceed down the start arm and into either the left or right arm to make 10 consecutive ambulatory decisions. D) CTRL rats made more right-hand than left-hand turns (B = 1.26, p <.001); PAE rats made an equivalent number of left-hand and right-hand turns. ***p < .001. Figure artwork created with BioRender.com.

Figure 3.. Sequential discrimination performance.

For rats in the SDSpace (solid-line enclosure) and SDTactile (dashed-line enclosure), the correct discrimination at each stage is depicted in green italic font. A) Regardless of discriminatory stimulus, rats in the prenatal alcohol exposure (PAE; n = 30) condition performed worse than control (CTRL; n = 31) animals in the simple discrimination (B = 16.49, p <.001). B) PAE rats performed worse during tactile IDREV1 compared to CTRL rats (B = 40.76, p <.001) and compared to PAE rat performance during spatial IDREV1 (B = 41.45, p <.001). C) There were no group differences during ED. D) Regardless of discriminatory stimulus, rats in the PAE condition performed worse than CTRL animals in the IDREV2. E) For PAE rats, the performance between SD and IDREV1 was equivalent but collectively worse than CTRL rats (B = 21.17, p <.01). F) PAE rats were significantly worse at shifting from the IDREV1 to the ED for rats in the SDSpace condition (B = 21.42, p <.01); PAE rats were significantly better at shifting from the IDREV1 to the ED for rats in the SDTactile condition (B = −24.38, p <.01). G) Performance between ED and IDREV2 was equivalent for PAE rats but collectively worse than CTRL rats (B = 19.79, p <.01). **p < .01, ***p < .001. Figure artwork created with BioRender.com.