Learning like a girl?“Estrogen modulates learning in female rats by acting directly at

distinct memory systems”

L. Zurkovsky et al.

Neuroscience (2007) 144: 26-37

* Set to be in print this January*

Background Information

• Research has shown that estrogen can influence learning and memory inconsistently…sometimes an enhancement is seen, other times and impairment.

• Explanatory theories include: efficacy of estrogen varies with motivating factors of the task; stress state of the animal; type of memory being investigated; duration and type of hormone administration….or maybe…

• Variation in effects may result from “estrogen biasing”.

• Estrogen may effect the relative contributions of different memory systems during cognition…causing a change in a learning strategy employed by the animal to solve a task.

• Previous research has shown in a dual solution appetitive T-maze task, estrogen elevated rats use place strategy and rats with low estrogen levels prefer response strategy.

• This suggests differing levels in estrogen may select a learning strategy preferentially as the result of activating different memory systems.

Place Strategy

• Is considered hippocampus sensitive learning strategy.

• Makes use of external cues and landmarks to complete appetitive tasks and learn relative location to reward.

Response Strategy

• Hippocampus insensitive learning strategy…rather a dorsal striatum sensitive strategy.

• Animal completes appetitive task by learning how to obtain reward by turning body in specific directions, not relying on external cues like landmarks.

Hypothesis

• The goal of this paper was to determine if estrogen acts on the hippocampus and striatum in an interactive or independent manner to effect learning strategy

Experimental Procedure

• 3 month old Sprague-Dawley female rats were used.

• Rats underwent a bilateral ovariectomy 21 days before behavioural training.

• Rats received a bilateral infusion of treatment or vehicle at 48, 24, and 2 hours prior to training via a cannula implanted in to the striatum or hippocampus.

• Control groups that were unimplanted, and ovariectomized were used as well to account for damage occurring from the implantation.

Procedure continued

• The estrogen used was 17-beta estradiol-3-sulphate in an artificial cerebral spinal fluid vehicle. Control rats received just the aCSF.

• Rats were food restricted to 85% of the free feeding weight + 5g to account for normal growth. Food deprivation necessary for appetitive tasks.

Maze Tasks

• A Y maze was used. Animal was placed in start arm and allowed to choose which arm to explore. If it entered the correct arm with the food reward, it was allowed to eat for 10 seconds before removal.

• If the incorrect arm was chosen the rat was removed from the maze.

• The reward was Frosted Cheerios.• Animals were trained until they were able to

make the correct choice nine times out of ten.

Place Task

• Followed previously described training protocol.

• Throughout training the reward remained at a fixed location relative to the extra-maze cues .

• The maze was rotated randomly by 120 degrees intervals to reduce employment of intra-maze cues.

Response task

• Again, the same protocol was used.

• Rats were rewarded for making a specific turn, left or right to find the Cheerios.

• The maze was again rotated to reduce use of intramaze cues.

Response task – cue poor

• Was identical to the previous response task, except a beige curtain was closed around the maze so that visual cues from the room could not be used.

Results

Results

Results

• Place learning was enhanced by administration of estrogen to the hippocampus, but was not significantly affected by estrogen treated striatum.

Results

Results

Results

• Response learning was impaired by striatal treatment with estrogen, but not by hippocampal treatment.

• These impairments only became statistically significant when visual cues were reduced…as seen in the next two slides.

Results

Results

What does it all mean?

• Data suggest that estrogen acts on distinct neural structures to regulate actions in two maze tasks that differ in cognitive learning strategy needed to obtain the reward.

• This suggests independent actions at the hippocampus and striatum…not integrative.

• Estrogen on hippocampus enhanced place learning.

• Estrogen on striatum impaired response learning.

• The effects on place learning are supported by research demonstrating the effects on estrogen on hippocampal neurochemistry

• The impairment of response learning is less easily explained but may be due to downstream regulation of dopamingergic activity, cholinergic function, or glutamatergic functions in the striatum.

Implications and Further Research

• Could have implications on sex differences in learning and strategy in areas of navigation and spatial memory.

• Implications on cognitive abilities during hormonal changes like puberty and menopause.

• Hippocampal and striatum sensitive tasks do employ other areas of the brain including the amygdala and frontal cortex…need to examine these structures to fully understand the effects of estrogen on learning strategy and cognition.