Telencephalic neurocircuitry and synaptic plasticity in rodent spatial learning and memory

doi:10.1016/j.brainres.2015.01.015

Brain Research

Volume 1621, 24 September 2015, Pages 294-308

https://doi.org/10.1016/j.brainres.2015.01.015 Get rights and content

Highlights

•
Rodent spatial learning and memory is equivalent to human episodic declarative memory.
•
Telencephalic neurocircuitry (TNC) is critical for rodent spatial learning and memory.
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Synaptic plasticity underlies this TNC involvement in rodent spatial learning.
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Valid and reliable research on brain disorders should focus on TNC-dependent learning.

Abstract

Spatial learning and memory in rodents represent close equivalents of human episodic declarative memory, which is especially sensitive to cerebral aging, neurodegeneration, and various neuropsychiatric disorders. Many tests and protocols are available for use in laboratory rodents, but Morris water maze and radial-arm maze remain the most widely used as well as the most valid and reliable spatial tests. Telencephalic neurocircuitry that plays functional roles in spatial learning and memory includes hippocampus, dorsal striatum and medial prefrontal cortex. Prefrontal–hippocampal circuitry comprises the major associative system in the rodent brain, and is critical for navigation in physical space, whereas interconnections between prefrontal cortex and dorsal striatum are probably more important for motivational or goal-directed aspects of spatial learning. Two major forms of synaptic plasticity, namely long-term potentiation, a lasting increase in synaptic strength between simultaneously activated neurons, and long-term depression, a decrease in synaptic strength, have been found to occur in hippocampus, dorsal striatum and medial prefrontal cortex. These and other phenomena of synaptic plasticity are probably crucial for the involvement of telencephalic neurocircuitry in spatial learning and memory. They also seem to play a role in the pathophysiology of two brain pathologies with episodic declarative memory impairments as core symptoms, namely Alzheimer’s disease and schizophrenia. Further research emphasis on rodent telencephalic neurocircuitry could be relevant to more valid and reliable preclinical research on these most devastating brain disorders.

This article is part of a Special Issue entitled SI: Brain and Memory.

Introduction

Learning is often seen as a process of behavioral change resulting from experience, which includes cognitive as well as motivational aspects. Memory, on the other hand, is the capacity to retain and recall facts, previous experiences, events, impressions, etc. (Markovitsch, 2000). Neuropsychologists classically distinguish between declarative (explicit) and non-declarative (implicit, procedural) memory. Although these terms refer to the ability to speak, both aspects of memory have been identified and modeled in animals as well. Declarative memory comprises semantic and episodic subsystems (Tulving, 1984). The latter refers to the (conscious) recollection of experiences (i.e., what, where and when), and has been found to be especially sensitive to cerebral aging, neurodegeneration, and various neuropsychiatric diseases (Pause et al., 2013).

The identification of complex cognitive abilities in animals that are analogous, homologous or precursory to essentially human functions remains controversial. However, most researchers consider spatial learning and memory in rodents to be at least a close equivalent of human declarative memory abilities (see Morellini, 2013). Spatial memory generally refers to information about the spatial properties of the environment, which is crucial for an animal’s ability to navigate in space, and has obvious ecological importance for heavily predated and burrowing murid species.

Section snippets

Spatial learning and memory tests in laboratory rodents

Researchers devised hundreds of arenas and protocols to investigate spatial learning and memory in laboratory rodents. However, Morris water maze (MWM) and radial-arm maze (RAM) remain the most widely used. We will briefly review these two tests below, but refer to Hodges (1996) for a thorough comparison between them.

First described by Morris in the early 1980s, MWM consists of a pool filled with opaque water with a submerged escape platform (Morris, 1984, D’Hooge and De Deyn, 2001). In order

Involvement of telencephalic structures in spatial learning and memory

Declarative memory impairments have been historically described in patients with hippocampal damage. Hippocampus (HC) and its adjacent entorhinal (EC), perirhinal and parahippocampal cortices have been shown to play a crucial role in declarative and spatial memory abilities (Moser et al., 2008, Squire, 2009, Eichenbaum, 2013). In rodents, HC lesions impair spatial learning and memory in the MWM (Morris, 1984, Moser et al., 1993, Devan and White, 1999), as well as in RAM and other spatial tasks (

Telencephalic neurocircuitry in spatial learning and memory

We have seen that telencephalic structures such as HC, several areas of the mPFC, and DMS are critical for specific aspects of spatial learning and memory. Researchers argue, however, that most of the brain is involved in spatial learning some way or another, and that the brain contains different systems that collaborate in a serial or parallel fashion. Many telencephalic areas have overlapping or complementary functions, and their interaction is of equal, if not greater importance than their

Spatial learning-related synaptic plasticity in telencephalic structures

Hebb (1949) historically postulated that associative memories are formed by a process that strengthens synaptic connections. It is now widely accepted that experience modifies behavior through activity-dependent, long-lasting synaptic modifications (Hölscher, 1999). Notably, the two major forms of synaptic plasticity, namely long-term potentiation (LTP), a lasting increase in synaptic strength between simultaneously activated neurons (Bliss and Collingridge, 1993), and long-term depression

Brain disorders that affect telencephalic neurocircuitry and spatial learning

Disturbances of memory functions are core pathological and diagnostic features of many brain disorders (Huber and Paulson, 1985, Förstl and Kurz, 1999, Kenworthy et al., 2008, van Os and Kapur, 2009, Pagonabarraga and Kulisevsky, 2012, Stretton and Thompson, 2012). Episodic declarative memory functions are particularly susceptible to the effects of ageing and neurodegeneration (McIntyre and Craik, 1987, Gabrieli, 1996). We will presently focus on two severe disorders of telencephalic

Spatial learning and synaptic plasticity in AD models

AD is characterized by cortical atrophy, synaptic loss and neuronal cell death, neuro-inflammation, and the accumulation of amyloid plaques and tau protein-based neurofibrillary tangles (Holtzman et al., 2011). Since AD patients display progressive cognitive decline, attributed to loss of synapses and neurons in HC and other telencephalic structures, valid animal models should reproduce such deficits. MWM consequently became the golden standard test in AD mouse models. Table 1 summarizes

Spatial learning and synaptic plasticity in schizophrenia models

Schizophrenia patients display pathognomonic positive and negative symptoms as well as cognitive deficits (Simpson et al., 2010). Cognitive defects best predict functional outcome in these patients (Green et al., 2004, Harvey et al., 2004), but remain mostly intractable with the available therapeutics (Papaleo et al., 2012). Visual learning and memory are one of 7 cognitive domains that are affected in schizophrenia (Green et al., 2004). Valid schizophrenia models should definitely mimic at

Conclusion

Rodent spatial learning and memory reliably models human episodic declarative memory abilities. MWM and RAM are definitely the most widely used tests of spatial learning and memory in laboratory rodent. The repertoire of sensitive tools to measure cognitive and behavioral changes in preclinical models remains a crucial, but often overlooked element in preclinical research on neurodevelopmental and neurodegenerative disorders.

Telencephalic neurocircuitry that plays functional roles in rodent

Acknowledgments

TP is a doctoral student of the Flemish science and technological development fund IWT-Vlaanderen, AVdJ is a post-doctoral fellow of the Flemish science fund FWO-Vlaanderen. The authors also received major financial support from a research program on complex learning of the KU Leuven research board (GOA project with RD as main promoter). The authors wish to thank Julie Puttemans for artwork.

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The use of an allocentric strategy also depends on both structures, but transiently. Indeed, following sustained training, the DStr is no longer needed for navigation correction, but it seems important for the acquisition of a spatial approach to a task (Jacobson, Gruenbaum, & Markus, 2012; Pooters, Van der Jeugd, Callaerts-Vegh, & D'Hooge, 2015, 2016). In case of a repetitive navigation task with full access to allothetic cues, the DHip appears more crucial than the DStr, first to enable a preferential engagement of the response memory-based system for up to 6 training days, and later on, between 6 and 14 days, to use the place memory-based system.
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Throughout learning this group failed to develop a preference for the target quadrant (t-test, all P-values ≥ 0.20 for probe 2 and 3), whereas DLS and sham animals spent significantly more time in the platform quadrant from the second training week (t-test, all P-values ≤ 0.01 for probe 2 and 3). Recent literature suggests that the two subdivisions of the dorsal striatum (DMS and DLS) play different roles in cognitive performance in general, and spatial learning and memory in particular [12]. In the current study, we further examined the differential involvement of DMS and DLS in the MWM task, the dominant paradigm to investigate spatial learning and memory in laboratory rodents [10,32].
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¹: These authors contributed equally to the manuscript.

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Research ReportTelencephalic neurocircuitry and synaptic plasticity in rodent spatial learning and memory

Highlights

Abstract

Introduction

Section snippets

Spatial learning and memory tests in laboratory rodents

Involvement of telencephalic structures in spatial learning and memory

Telencephalic neurocircuitry in spatial learning and memory

Spatial learning-related synaptic plasticity in telencephalic structures

Brain disorders that affect telencephalic neurocircuitry and spatial learning

Spatial learning and synaptic plasticity in AD models

Spatial learning and synaptic plasticity in schizophrenia models

Conclusion

Acknowledgments

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A comparison of the effects of medial prefrontal, cingulate cortex and cingulum bundle lesion on tests of spatial memory: evidence of a double dissociation between frontal and cingulum bundle conditions

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Learn. Mem.

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Research Report
Telencephalic neurocircuitry and synaptic plasticity in rodent spatial learning and memory