Glutamate infused posttraining into the hippocampus or caudate-putamen differentially strengthens place and response learning

Abstract

A cross-maze task that can be acquired through either place or response learning was used to examine the hypothesis that posttraining neurochemical manipulation of the hippocampus or caudate-putamen can bias an animal toward the use of a specific memory system. Male Long-Evans rats received four trials per day for 7 days, a probe trial on day 8, further training on days 9 -15, and an additional probe trial on day 16. Training occurred in a crossmaze task in which rats started from a consistent start-box (south), and obtained food from a consistent goal-arm (west). On days 4 -6 of training, rats received posttraining intrahippocampal (1 g͞0.5 l) or intracaudate (2 g͞0.5 l) injections of either glutamate or saline (0.5 l). On days 8 and 16, a probe trial was given in which rats were placed in a novel start-box (north). Rats selecting the west goal-arm were designated ''place'' learners, and those selecting the east goal-arm were designated ''response'' learners. Saline-treated rats predominantly displayed place learning on day 8 and response learning on day 16, indicating a shift in control of learned behavior with extended training. Rats receiving intrahippocampal injections of glutamate predominantly displayed place learning on days 8 and 16, indicating that manipulation of the hippocampus produced a blockade of the shift to response learning. Rats receiving intracaudate injections of glutamate displayed response learning on days 8 and 16, indicating an accelerated shift to response learning. The findings suggest that posttraining intracerebral glutamate infusions can (i) modulate the distinct memory processes mediated by the hippocampus and caudate-putamen and (ii) bias the brain toward the use of a specific memory system to control learned behavior and thereby influence the timing of the switch from the use of cognitive memory to habit learning to guide behavior. A ccording to the ''multiple memory systems'' hypothesis, different forms of memory are organized in independent brain systems. This hypothesis is supported by studies involving several mammalian species, including rats (1-6), monkeys (7-10), and humans (11)(12)(13)(14). For example, in rats, findings from double-dissociation experiments using lesion (3-6, 15) and posttraining intracerebral drug injection techniques (16)(17)(18)(19) indicate that the hippocampal system and caudate-putamen are parts of independent memory systems.Characteristics of the psychological operating principles that distinguish multiple memory systems have been proposed by numerous investigators (e.g., refs. 1, 2, 8, 9, 11, 13, 20, and 21), and the design of each of these theories, particularly those derived from animal research, has been influenced to some extent by the historical debate between ''cognitive'' and ''stimulus-response'' (S-R) animal learning theorists. The cognitive view, exemplified by the early work of Tolman (22,23), holds that animals acquire knowledge-based expectations that serve to guide behavior in a purposeful manner, a form of learning in which relatio...

Spatial Memory Deficits Induced by Perinatal Treatment of Rats with PCP and Reversal Effect of D-Serine

“…D-Serine permitted the disrupted animals to use a proper allocentric strategy, instead of a compensatory idiocentric strategy, and permitted the restructuring of the proper spatial mapping process. Similar facilitation of the allocentric strategy has been described in adult rats receiving local intrahippocampal injection of glutamate (Packard, 1999), showing that increasing glutamatergic activity facilitates spatial mapping abilities of rats.…”

Task-Dependent Role for Dorsal Striatum Metabotropic Glutamate Receptors in Memory

“…Consistent with this hypothesis, post-training intradorsal striatal infusions of glutamate selectively enhance memory in a visibleplatform water maze task in which rats are trained to approach a cued escape platform that is located in a different maze location on each trial (Packard and Teather 1999). Intradorsal striatal injections of glutamate also enhance response learning in a cross-maze task in which a specific body-turn direction is consistently reinforced (Packard 1999).…”

“…The dorsal striatum is hypothesized to be selectively involved in stimulus-response (S-R) learning and memory (for an early proposal involving nonhuman primates, see Mishkin and Petri [1984]), a view supported by findings of task-dependent effects (i.e., double dissociations) following lesion (Packard et al 1989;Packard and McGaugh 1992;Kesner et al 1993;McDonald and White 1993) or post-training drug manipulations of this structure (Packard and White 1991;Packard andTeather 1997, 1999;Packard 1999). It has been suggested that glutamatergic input to the dorsal striatum provides, in part, sensory information underlying the formation of S-R associations (White 1989).…”

“…However, lesion studies implicate the dorsal striatum in acquisition of inhibitory avoidance and visible-platform water maze tasks (e.g., Neill and Grossman 1971;Winocur 1974;Packard and McGaugh 1992;McDonald and White 1994), providing converging evidence consistent with the hypothesis that the drug infusions acted within the dorsal striatum to affect memory consolidation in this study. Other post-training drug infusion studies also indicate a time-dependent role for the dorsal striatum in memory-consolidation processes in inhibitory avoidance and visible-platform water maze tasks (e.g., Prado-Alcala et al 1981;Packard et al , 1996Packard andTeather 1997, 1999).…”

Blunted hippocampal, but not striatal, acetylcholine efflux parallels learning impairment in diencephalic-lesioned rats

“…Previous research using a delayed alternation task demonstrated that rats start out typically using a place strategy early in maze training and later switch to a response strategy (Packard, 1999) and this is related to elevated ACh levels in the hippocampus and striatum, respectively (Chang & Gold, 2003b;Pych et al, 2005a;Pych, Chang, ColonRivera, Haag, & Gold, 2005b). The NMTP task is different from spontaneous and delayed alternation in that the to-be-remembered place changes in a random fashion from trial-to-trial.…”