Fornix Lesions Decouple the Induction of Hippocampal Arc Transcription from Behavior But Not Plasticity

Fletcher, Bonnie R.; Calhoun, Michael E.; Rapp, Peter R.; Shapiro, Matthew L.

doi:10.1523/jneurosci.4441-05.2006

Cited by 49 publications

(42 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cold Spring Harbor Laboratory Press on May 10, 2018 -Published by learnmem.cshlp.org Downloaded from likely to have impaired the stable maintenance of IA traininginduced LTP. Such IA-associated LTP within area CA1 is widely distributed (Whitlock et al 2006), consistent with theoretical and previous experimental mapping studies suggesting that IA and other forms of learning engage widely distributed neural circuits throughout hippocampus (Buzsaki et al 1990;Treves and Rolls 1994;Guzowski et al 1999;Taubenfeld et al 2001;de Hoz et al 2005;Fletcher et al 2006). Our experiments here showing that the maintenance of LTP was impaired up to ∼1200 µm from the site of the inhibitor infusion suggest that acute interference with synaptic plasticity mechanisms over a spatially limited extent within dorsal hippocampus has significant effects on behavioral performance.…”

Section: Discussionsupporting

confidence: 89%

The extracellular protease matrix metalloproteinase-9 is activated by inhibitory avoidance learning and required for long-term memory

Nagy¹,

Bozdagi²,

Huntley³

2007

Learn. Mem.

View full text Add to dashboard Cite

Matrix metalloproteinases (MMPs) are a family of extracellularly acting proteolytic enzymes with well-recognized roles in plasticity and remodeling of synaptic circuits during brain development and following brain injury. However, it is now becoming increasingly apparent that MMPs also function in normal, nonpathological synaptic plasticity of the kind that may underlie learning and memory. Here, we extend this idea by investigating the role and regulation of MMP-9 in an inhibitory avoidance (IA) learning and memory task. We demonstrate that following IA training, protein levels and proteolytic activity of MMP-9 become elevated in hippocampus by 6 h, peak at 12-24 h, then decline to baseline values by ∼72 h. When MMP function is abrogated by intrahippocampal infusion of a potent gelatinase (MMP-2 and MMP-9) inhibitor 3.5 h following IA training, a time prior to the onset of training-induced elevation in levels, IA memory retention is significantly diminished when tested 1-3 d later. Animals impaired at 3 d exhibit robust IA memory when retrained, suggesting that such impairment is not likely attributed to toxic or other deleterious effects that permanently disrupt hippocampal function. In anesthetized adult rats, the effective distance over which synaptic plasticity is impaired by a single intrahippocampal infusion of the MMP inhibitor of the kind that blocks IA memory is ∼1200 µm. Taken together, these data suggest that IA training induces a slowly emerging, but subsequently protracted period of MMP-mediated proteolysis critical for enabling long-lasting synaptic modification that underlies long-term memory consolidation.New information is learned and remembered through functional and structural modifications of synaptic connections (Bliss and Collingridge 1993;Rogan et al. 1997;Rioult-Pedotti et al. 1998Jorntell and Hansel 2006;Pastalkova et al. 2006;Whitlock et al. 2006). Several kinds of learning and memory tasks have been shown to drive changes in neurotransmitter receptor function and/or localization (Cammarota et al. 1995;Bevilaqua et al. 2005;Rumpel et al. 2005;Whitlock et al. 2006), as well as induce over time changes in synapse number or morphology (O'Malley et al. 2000;Geinisman et al. 2001;Eyre et al. 2003;Leuner et al. 2003;Maviel et al. 2004;Lamprecht et al. 2006;Rekart et al. 2007). These observations suggest that there must be learninginduced cellular mechanisms for coordinating functional and structural remodeling of synaptic connectivity to enable longterm memory, but there is little known about the molecules that could fulfill such a role.Learning-related, regulated extracellular proteolysis could be one mechanism for coordinating functional and structural synaptic plasticity, thereby enabling memory (Huang et al. 1996;Madani et al. 1999;Calabresi et al. 2000;Pawlak et al. 2002;Tamura et al. 2006). It is well-recognized that extracellular matrix (ECM) proteins as well synaptic cell adhesion molecules contribute to both functional and structural aspects of synaptic plasticity, are modified by l...

show abstract

Section: Discussionsupporting

confidence: 89%

The extracellular protease matrix metalloproteinase-9 is activated by inhibitory avoidance learning and required for long-term memory

Nagy¹,

Bozdagi²,

Huntley³

2007

Learn. Mem.

View full text Add to dashboard Cite

show abstract

“…With respect to gene function, a number of IEGs that may be importantly involved in both synaptic plasticity and memory have now been identified (Guzowski, 2002). Among these, Arc (activityregulated cytoskeletal-associated protein) has received considerable recent attention (Bramham et al, 2010;Shepherd and Bear, 2011), in part because it is more tightly coupled to the induction of synaptic plasticity than to neuronal activity per se (Fletcher et al, 2006). Importantly, Arc is one of the only IEGs whose mRNA is rapidly transported to activated synaptic zones, where it undergoes local protein synthesis and associates with dendritic cytoskeletal proteins (Link et al, 1995;Lyford et al, 1995;Steward et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, Arc is one of the only IEGs whose mRNA is rapidly transported to activated synaptic zones, where it undergoes local protein synthesis and associates with dendritic cytoskeletal proteins (Link et al, 1995;Lyford et al, 1995;Steward et al, 1998). Moreover, Arc expression in hippocampus is rapidly and robustly enhanced following a number of behavioral manipulations, including novel environment exploration and spatial learning (Guzowski et al, 2001;Kelly and Deadwyler, 2002;Fletcher et al, 2006), while inhibiting hippocampal Arc translation with antisense oligodeoxynucleotides (ODNs) blocks both late-phase LTP and the consolidation of some forms of memory in both the hippocampus and amygdala (Guzowski et al, 2000;Ploski et al, 2008); similar patterns of physiological and behavioral data are observed in Arc knock-out mice .…”

Section: Introductionmentioning

confidence: 99%

The Importance of Having Arc: Expression of the Immediate-Early Gene Arc Is Required for Hippocampus-Dependent Fear Conditioning and Blocked by NMDA Receptor Antagonism

Czerniawski¹,

Ree²,

Chia³

et al. 2011

J. Neurosci.

View full text Add to dashboard Cite

Long-lasting, experience-dependent changes in synaptic strength are widely thought to underlie the formation of memories. Many forms of learning-related plasticity are likely mediated by NMDA receptor activation and plasticity-related gene expression in brain areas thought to be important for learning and memory, including the hippocampus. Here, we examined the putative role of activity-regulated cytoskeletal-associated protein (Arc), an immediate-early gene (IEG) whose expression is tightly linked to the induction and maintenance of some forms of neuronal plasticity, in hippocampus-dependent and hippocampus-independent forms of learning. The extent to which learning-induced Arc expression may depend on NMDA receptor activation was also assessed. First, we observed an increase in Arc gene and protein products in both dorsal hippocampus (DH) and ventral hippocampus (VH) of male Sprague Dawley rats after hippocampusdependent trace and contextual fear conditioning, but not after hippocampus-independent delay fear conditioning. Specific knockdown of Arc using antisense oligodeoxynucleotides (ODNs) in DH or VH attenuated the learning-related expression of Arc protein, and resulted in a dramatic impairment in trace and contextual, but not delay, fear conditioning. Finally, pretraining infusions of the NMDA receptor antagonist APV into the DH or VH blocked the learning-induced enhancement of Arc in a regionally selective manner, suggesting that NMDA receptor activation and Arc translation are functionally coupled to support hippocampus-dependent memory for fear conditioning. Collectively these results provide the first evidence suggesting that NMDA receptor-dependent expression of the IEG Arc in both DH and VH likely underlies the consolidation of a variety of forms of hippocampus-dependent learning.

show abstract

“…Although memory consolidation requires expression of immediate early genes like Arc (10,(13)(14)(15), it is unknown if Arc is required for plasticity in cortical regions that lack stimulus-induced activity. Although Arc expression has been observed with high levels of neuronal activity (16)(17)(18)(19)(20)(21), such activity is not always sufficient (22)(23)(24). Direct tests linking Arc expression to neural activity require control over neural activity in a topographically specific manner, or a simultaneous assessment of action potential activity and Arc expression on a neuron-byneuron basis.…”

mentioning

confidence: 99%

Arc expression and neuroplasticity in primary auditory cortex during initial learning are inversely related to neural activity

Carpenter-Hyland

Plummer

Vazdarjanova

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Models of learning-dependent sensory cortex plasticity require local activity and reinforcement. An alternative proposes that neural activity involved in anticipation of a sensory stimulus, or the preparatory set, can direct plasticity so that changes could occur in regions of sensory cortex lacking activity. To test the necessity of target-induced activity for initial sensory learning, we trained rats to detect a low-frequency sound. After learning, Arc expression and physiologically measured neuroplasticity were strong in a high-frequency auditory cortex region with very weak target-induced activity in control animals. After 14 sessions, Arc and neuroplasticity were aligned with target-induced activity. The temporal and topographic correspondence between Arc and neuroplasticity suggests Arc may be intrinsic to the neuroplasticity underlying perceptual learning. Furthermore, not all neuroplasticity could be explained by activity-dependent models but can be explained if the neural activity involved in the preparatory set directs plasticity.rat | instrumental learning | neurophysiology T he brain's ability to modify its own structure and function is currently used in diverse therapies involving remediation of language-learning impairment, reversing age-related cognitive decline, stroke rehabilitation, and others. These powers of neuroplasticity stem from the mammalian brain's ability to reorganize in response to experience (1-4). In sensory cortex, plasticity induced by sensory tasks optimizes the brain's capacity for future performance through amplifying activity that is most informative about reinforcement (4-6). Dominant models of this plasticity are activity-dependent (2,7,8), and associated learning is presumed to be a function of endogenous processes reliant on gene activation, because long-term plasticity and long-term memory require protein synthesis (9) following expression of immediate-early genes such as Arc (10, 11). Although models of sensory cortex plasticity are dependent on activity, these models fail to account for plasticity and behavioral phenomena observed shortly after learning.A prediction of activity-dependent models is that the strongest and most selective population responses to a target stimulus should grow the most. However, in contrast to this prediction, cortical patterns of activity early after learning enter a weakly selective and highly responsive state that is subsequently refined into a highly selective and less responsive state (3). The same phenomenon is reflected behaviorally. If auditory stimuli are paired with nucleus basalis stimulation, acoustically induced changes in respiratory rate can initially be induced by a wide range of sound frequencies, and these induced respiratory changes become more frequency-specific with time (12). These findings suggest that cortical regions representing sensory stimuli other than the learned sensory stimulus may be recruited in brain plasticity shortly after learning. This conclusion contrasts with activity-dependent models. Although memor...

show abstract

Fornix Lesions Decouple the Induction of Hippocampal Arc Transcription from Behavior But Not Plasticity

Cited by 49 publications

References 46 publications

The extracellular protease matrix metalloproteinase-9 is activated by inhibitory avoidance learning and required for long-term memory

The extracellular protease matrix metalloproteinase-9 is activated by inhibitory avoidance learning and required for long-term memory

The Importance of Having Arc: Expression of the Immediate-Early Gene Arc Is Required for Hippocampus-Dependent Fear Conditioning and Blocked by NMDA Receptor Antagonism

Arc expression and neuroplasticity in primary auditory cortex during initial learning are inversely related to neural activity

Contact Info

Product

Resources

About