Training-induced elevations in extracellular lactate in hippocampus and striatum: Dissociations by cognitive strategy and type of reward

Abstract

Recent evidence suggests that astrocytes convert glucose to lactate, which is released from the astrocytes and supports learning and memory. This report takes a multiple memory perspective to test the role of astrocytes in cognition using real-time lactate measurements during learning and memory. Extracellular lactate levels in the hippocampus or striatum were determined with lactate biosensors while rats were learning place (hippocampus-sensitive) or response (striatum-sensitive) versions of T-mazes. In the first experiment, rats were trained on the place and response tasks to locate a food reward. Extracellular lactate levels in the hippocampus increased beyond those of feeding controls during place training but not during response training. However, striatal lactate levels did not increase beyond those of controls when rats were trained on either the place or the response version of the maze. Because food ingestion itself increased blood glucose and brain lactate levels, the contribution of feeding may have confounded the brain lactate measures. Therefore, we conducted a second similar experiment using water as the reward. A very different pattern of lactate responses to training emerged when water was used as the task reward. First, provision of water itself did not result in large increases in either brain or blood lactate levels. Moreover, extracellular lactate levels increased in the striatum during response but not place learning, whereas extracellular lactate levels in the hippocampus did not differ across tasks. The findings from the two experiments suggest that the relative engagement of the hippocampus and striatum dissociates not only by task but also by reward type. The divergent lactate responses of the hippocampus and striatum in place and response tasks under different reward conditions may reflect ethological constraints tied to foraging for food and water.

Extracellular levels of glucose in the hippocampus and striatum during maze training for food or water reward in male rats

“…during training above what results from reward alone was clearly evident in waterrewarded rats and for hippocampus with food reward but did not reach significance in food-rewarded trained rats. We have previously reported in untrained rats that food, but not water, intake increases blood glucose [59], suggesting that food rewards alone may have masked training-related increases in glucose during training. However, the use of water reward makes it clear that glucose levels in both the hippocampus and striatum increase as a consequence of place or response training, rather than increasing as a direct function of reward-induced changes in blood glucose levels.…”

“…Small burr holes were made in the skull overlying the hippocampus or striatum for guide cannulae (9 mm long, 350 µm diameter, BASi, West Lafayette, IN) and more laterally for hardware to attach the headcap. To permit the later insertion of a glucose biosensors near the time of training, the guide cannulae were placed just dorsal to the hippocampus (AP: -3.8 mm from bregma, ML: + or -2.5 mm, 0.9 mm ventral to dura) or striatum (AP: 0.2 mm from bregma, ML: + or -2.0 mm, 1.5 mm ventral to dura, angled 15 degrees away from midline) [59]. The angled approach for the striatum cannulae was needed to accommodate the head stage and later insertion of glucose biosensors [see 59].…”

“…On the training day, each rat was placed in the testing room and allowed to acclimate to the room for approximately one hour. A four-arm radial maze was used with one arm blocked, forming a T-shaped maze as used and detailed in past papers [40,59,[61][62]. The arms of the maze were 45 cm long x 14 cm wide x 7.5 cm high and extended from a 14 cm 2 center area.…”

“…One of the mechanisms through which brain glucose might regulate learning and memory is by contributing to astrocytic production and release of lactate into extracellular fluid [2,3,14,[52][53][54][55][56][57][58][59][60]. Recently, we studied the responses of extracellular lactate while rats were trained on place and response mazes [59] that used either food or water as reward. With food reward, extracellular lactate levels increased beyond those of feeding controls during place but not response training, but striatal levels did not exceed the increases in controls for either maze.…”

“…Because lactate is derived from glucose, largely in astrocytes, the present study examined changes in glucose in the hippocampus and striatum under training and reward conditions matching those of the previous study with lactate [59] to compare and contrast the responses of the two energy substrates to training. In particular, we assessed whether changes in extracellular glucose levels during training would vary in a task by reward manner similar to the results seen with lactate, thereby supporting the view that glucose and lactate are sequentially linked to effects on learning and memory.…”