Bidirectional Competition Between Striatum and Hippocampus During Learning

The "dry cleaning effect" paper was finally published online Monday Oct 27 at PNAS, a full week after the initial press release. To briefly review:

'Dry cleaning effect' explained by forgetful Yale researcher

Yale researchers have described how dueling brain systems may explain why you forget to drop off the dry cleaning and may point to ways that substance abusers and people with OCD can overcome bad habits.

In Proceedings of the National Academy of Sciences, Christopher J. Pittenger, M.D., and colleagues describe a sort of competition between areas of the brain involved in learning that results in what Pittenger calls the "dry cleaning effect."

At the time, The Neurocritic scoffed at the overreach of the authors in interpreting their data for the press, but at the same time acknowledged that the actual paper could be sound.

Call me humanocentric, but I think distractibility (and the frontal lobes) might have a role in this sort of absentmindedness. Nevertheless, the study itself could be perfectly reasonable, and the results sound interesting...

But what does the paper actually say? What were the experimental tasks and manipulations? To begin with, the authors (Lee et al., 2008) adopted the multiple memory systems perspective (e.g., Squire 2004) that views different types of learning and memory (e.g., spatial learning and stimulus-response learning) as subserved by dissociable brain circuits (which include the hippocampus and the dorsal striatum, respectively). That's nothing new. In rodents, these two types of learning and memory are differentially affected by damage to the hippocampus and striatum in the fashion of a "double dissociation"¹ -- lesions to the hippocampus impair spatial learning but not S-R learning, while lesions to the dorsal striatum impair S-R learning but not spatial learning. This is true in humans as well, where (more broadly speaking) hippocampal damage impairs declarative memory but not procedural memory, and striatal damage impairs procedural memory but not declarative memory.

So what is new here? The way these two systems interact with each other is not fully understood. However (as cited by the authors), neuroimaging studies in humans indicate that hippocampal and striatal activity during spatial navigation (for example) shows an inverse relationship (Hartley et al., 2003),² raising the possibility that the two systems compete with each other.³ And as far as competition goes, it's quite well-known that habit learning is suppressed by other learning mechanisms, even in flies (Brembs et al., submitted). Brembs goes on to state in his comment on the dry cleaning post:

What I thought was surprising was that apparently the habit learning striatum also inhibited spatial learning, which is something I have never heard about.

Or as Lee et al. put it in their Introduction:

In rodents, hippocampal lesions can enhance acquisition of a striatum-dependent win-stay behavioral strategy in a radial arm maze task, perhaps by removing competitive interference from spatial information.

To date, however, we are aware of no studies that have provided clear evidence for interference by striatum-dependent processes on hippocampus-dependent learning; as a result, it remains unclear whether there is true bi-directional competition between these learning systems.

Their methods? Cued and spatial learning were assessed in mice with a modified water-maze task described in great detail in Fig S1 (which has a 588 word legend, not reproduced below).


Fig S1 (Lee et al. 2008).

From the main Methods section:

Briefly, animals learned to escape a pool of opaque water (similar to that used in the Morris water maze) by swimming to one of two visually distinct cues. ... Three distinct visible cues were used [plastic cylinders painted either solid gray or with black-and-white stripes...]

The first 5 days consisted of shaping to the task. On day -5, animals were placed on the platform four times (20-min inter-trial interval). On days -4 through -1, the escape platform was marked with the uniform gray cue; animals were placed in the pool and allowed 120 seconds to swim to it.

Following shaping, animals were trained in the two-cue task for 5 or 7 days; each animal was trained in either the cued or spatial task, never in both. All experiments consisted of four trials per day with a 20-min inter-trial interval. In the cued task, the escape platform was moved on each trial but was reliably marked by one of the two cues... In the spatial task, the escape platform was always in the same location but was variably associated with the two striped cues. In both tasks, the second visible cue (i.e., the lure) was present in a quadrant adjacent to the escape platform and its associated cue (i.e., the goal) on a stand that held it at an identical height in the water but did not permit escape. [NOTE: mean!]...

Learning was assayed by using a probe trial, administered in place of the fourth training trial after 3, 5, and/or 7 days of training... In the probe trial, both goal and lure cues were placed on stands that did not allow escape; the animal’s search was monitored by an overhead camera over 60 seconds. Extra-maze cues were identical to those present in a training trial. In both the cued and the spatial task, a systematic bias toward the goal cue relative to the lure cue (i.e., toward the location where the platform would have been on a regular training trial) was interpreted as evidence of learning.

Hopefully, it was not as difficult for the mice to learn the task as it is for the reader to understand what was done. On that note, to minimize the reader's cognitive load, the major results of the study are conveyed via the authors' paragraph subheadings.

Dorsal Striatal Lesions Impair Cued Learning and Enhance Spatial Learning.

Disruption of Striatal Synaptic Plasticity in Transgenic Mice Also Impairs Cued Learning and Enhances Spatial Learning.

KCREB Transgenic Mice Continue to Show Accelerated Learning upon Spatial Reversal.

Lesions of Dorsal Hippocampus Impair Spatial Learning and Potentiate Cued Learning.

And the conclusion? It's in the title: A double dissociation revealing bidirectional competition between striatum and hippocampus during learning.


Footnotes

¹ It must be noted here that not all researchers agree on the significance of a double dissociation. Although many take it as strong evidence of independent brain (or cognitive) systems, others disagree. For instance, Berry et al. (2008) state:

Do dissociations imply independent systems? In the memory field, the view that there are independent implicit and explicit memory systems has been predominantly supported by dissociation evidence. Here, we argue that many of these dissociations do not necessarily imply distinct memory systems. We review recent work with a single-system computational model that extends signal-detection theory (SDT) to implicit memory. SDT has had a major influence on research in a variety of domains. The current work shows that it can be broadened even further in its range of application. Indeed, the single-system model that we present does surprisingly well in accounting for some key dissociations that have been taken as evidence for independent implicit and explicit memory systems.

² I have to point out here that even this spatial navigation study in humans is not analogous to the true "dry cleaning effect" where distractibility, absentmindedness, and lapses of attention are key culprits.

³ It seems to be a somewhat different story for reversal learning (Shohamy et al., 2008).

References

Berry CJ, Shanks DR, Henson RN. (2008). A unitary signal-detection model of implicit and explicit memory. Trends Cog Sci. 12:367-73.

Hartley T, Maguire EA, Spiers HJ, Burgess N. (2003). The well-worn route and the path less traveled: distinct neural bases of route following and wayfinding in humans. Neuron 37:877-88.

A. S. Lee, R. S. Duman, C. Pittenger (2008). A double dissociation revealing bidirectional competition between striatum and hippocampus during learning Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0807749105

The multiple memory systems framework proposes that distinct circuits process and store different sorts of information; for example, spatial information is processed by a circuit that includes the hippocampus, whereas certain forms of instrumental conditioning depend on the striatum. Disruption of hippocampal function can enhance striatum-dependent learning in some paradigms, which has been interpreted as evidence that these systems can compete with one another in an intact animal. However, it remains unclear whether such competition can occur in the opposite direction, as suggested by the multiple memory systems framework, or is unidirectional. We addressed this question using lesions and genetic manipulations in mice. Impairment of dorsal striatal function with either excitotoxic lesions or transgenic inhibition of the transcription factor cAMP response element-binding protein, which disrupts striatal synaptic plasticity, impaired striatum-dependent cued learning but enhanced hippocampus-dependent spatial learning. Conversely, excitotoxic lesions of the dorsal hippocampus disrupted spatial learning and enhanced cued learning. This double dissociation demonstrates bidirectional competition that constitutes strong evidence for the parallel operation of distinct memory systems.

Shohamy D, Myers CE, Hopkins RO, Sage J, Gluck MA. (2008). Distinct Hippocampal and Basal Ganglia Contributions to Probabilistic Learning and Reversal. J Cog Neurosci. Sep 29. [Epub ahead of print].

The hippocampus and the basal ganglia are thought to play fundamental and distinct roles in learning and memory, supporting two dissociable memory systems. Interestingly, however, the hippocampus and the basal ganglia have each, separately, been implicated as necessary for reversal learning-the ability to adaptively change a response when previously learned stimulus-outcome contingencies are reversed. Here, we compared the contribution of the hippocampus and the basal ganglia to distinct aspects of learning and reversal. Amnesic subjects with selective hippocampal damage, Parkinson's subjects with disrupted basal ganglia function, and healthy controls were tested on a novel probabilistic learning and reversal paradigm. In this task, reversal can be achieved in two ways: Subjects can reverse a previously learned response, or, they can select a new cue during the reversal phase, effectively "opting out" of the reversal. We found that both patient groups were intact at initial learning, but differed in their ability to reverse. Amnesic subjects failed to reverse, and continued to use the same cue and response learned before the reversal. Parkinson's subjects, by contrast, opted out of the reversal by learning a new cue-outcome association. These results suggest that both the hippocampus and the basal ganglia support reversal learning, but in different ways. The basal ganglia are necessary for learning a new response when a previously learned response is no longer rewarding. The failure of the amnesic subjects to reverse their response or to learn a new cue is consistent with a more general role for the hippocampus in configural learning, and suggests it may also support the ability to respond to changes in cue-outcome contingencies.

Squire LR. (2004). Memory systems of the brain: a brief history and current perspective. Neurobiol Learn Mem. 82:171-7.