The broad long-term objectives of the proposed research include an increased understanding of the organization of memory in the mammalian brain, the neurochemical bases of different forms of memory, and the modulatory influences on multiple memory systems. These objectives will be accomplished through experimental linkage of two sets of previous findings: 1) the hippocampus and caudate nucleus are parts of independent brain systems, and 2) the amygdala plays a modulatory role in memory, and can influence both hippocampal-dependent and caudate-dependent memory processes.
The specific aims of the hypothesis include an examination of three primary hypotheses: 1) The ventral and dorsal regions of the pallidal complex of the brain represent additional anatomical components of the hippocampal and caudate nucleus memory systems, respectively. 2) Glutamatergic neurotransmission in the hippocampus and caudate nucleus is a critical component of the neurochemical bases of memory in these two systems. 3) The modulatory influence of the amygdala on memory involve dissociable effects on the hippocampal and caudate nucleus memory systems, and is mediated by amygdala output via the stria terminalis. The research design and methods combine central nervous system manipulations in rats, including neural inactivation (via injection of the local anesthetic lidocaine), and post-training intracerebral injections of glutamatergic agonist and antagonist drugs that are selective for NMDA, AMPA, kainate, and metabotropic receptor subtypes. The role of the pallidal complex, glutamatergic neurotransmission, and the modulatory influence of the amygdala in memory will be assessed in rats trained in either hippocampal-dependent spatial water and radial maze tasks, or caudate nucleus-dependent cued water and radial maze tasks. The separable roles of the hippocampal system and caudate nucleus in memory that has been established in rodents is also observable in humans with neurological disorders compromising these two brain regions. Thus, increased knowledge of the anatomical and neurochemical bases of multiple memory systems may have important implications for understanding the biological bases of human learning and memory.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
First Independent Research Support & Transition (FIRST) Awards (R29)
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Cognitive Functional Neuroscience Review Committee (CFN)
Program Officer
Anderson, Kathleen C
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Yale University
Schools of Arts and Sciences
New Haven
United States
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Hsu, Emily; Packard, Mark G (2008) Medial prefrontal cortex infusions of bupivacaine or AP-5 block extinction of amphetamine conditioned place preference. Neurobiol Learn Mem 89:504-12
Schroeder, Jason P; Packard, Mark G (2004) Facilitation of memory for extinction of drug-induced conditioned reward: role of amygdala and acetylcholine. Learn Mem 11:641-7
Packard, Mark G; Wingard, Jeffrey C (2004) Amygdala and ""emotional"" modulation of the relative use of multiple memory systems. Neurobiol Learn Mem 82:243-52
Schroeder, Jason P; Packard, Mark G (2003) Systemic or intra-amygdala injections of glucose facilitate memory consolidation for extinction of drug-induced conditioned reward. Eur J Neurosci 17:1482-8
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Hsu, Emily H; Schroeder, Jason P; Packard, Mark G (2002) The amygdala mediates memory consolidation for an amphetamine conditioned place preference. Behav Brain Res 129:93-100
Schroeder, Jason P; Packard, Mark G (2002) Posttraining intra-basolateral amygdala scopolamine impairs food- and amphetamine-induced conditioned place preferences. Behav Neurosci 116:922-7
Schroeder, Jason P; Wingard, Jeffrey C; Packard, Mark G (2002) Post-training reversible inactivation of hippocampus reveals interference between memory systems. Hippocampus 12:280-4
Alexander, Gerianne M; Packard, Mark G; Peterson, Bradley S (2002) Sex and spatial position effects on object location memory following intentional learning of object identities. Neuropsychologia 40:1516-22
Kim, J J; Lee, H J; Han, J S et al. (2001) Amygdala is critical for stress-induced modulation of hippocampal long-term potentiation and learning. J Neurosci 21:5222-8

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