Cell-type specific inactivation of hippocampal CA1 disrupts location-dependent object recognition in the mouse
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The allatostatin receptor (AlstR)/ligand inactivation system enables potent regulation of neuronal circuit activity. To examine how different cell types participate in memory formation, we have used this system through Cre-directed, cell-type specific expression in mouse hippocampal CA1 in vivo and examined functional effects of inactivation of excitatory vs. inhibitory neurons on memory formation. We chose to use a hippocampus-dependent behavioral task involving location-dependent object recognition (LOR). The double transgenic mice, with the AlstRs selectively expressed in excitatory pyramidal neurons or inhibitory interneurons, were cannulated, targeting dorsal hippocampus to allow the infusion of the receptor ligand (the allatostatin [AL] peptide) in a time dependent manner. Compared to control animals, AL-infused animals showed no long-term memory for object location. While inactivation of excitatory or inhibitory neurons produced opposite effects on hippocampal circuit activity in vitro, the effects in vivo were similar. Both types of inactivation experiments resulted in mice exhibiting no long-term memory for object location. Together, these results demonstrate that the Cre-directed, AlstR-based system is a powerful tool for cell-type specific manipulations in a behaving animal and suggest that activity of either excitatory neurons or inhibitory interneurons is essential for proper long-term object location memory formation.
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Dorsal hippocampus, and in particular CA1, has a greater role in memory functions.
“these data are in line with the greater role of memory functions subserved by dorsal hippocampus, and in particular by CA1 region25,75”
From Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress (2014) · cites this paper as [75]
Mice with specific inactivation of the hippocampal excitatory or inhibitory neurons exhibited long-term OPP deficits, suggesting that both excitatory and inhibitory neurons are cardinal for this memory.
“Mice with specific inactivation of the hippocampal excitatory or inhibitory neurons exhibited long-term OPP deficits, suggesting that both excitatory and inhibitory neurons are cardinal for this memory (Haettig et al., 2013).”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Haettig et al., 2013
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- Authors
- Haettig, J., Sun, Y., Wood, M. A., & Xu, X.
- Affiliations
- University of California, Irvine (US)
- Venue
- Learning & Memory
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2013-02-15
- Volume
- 20
- Issue
- 3
- Pages
- 139-146
- ISSN
- 1072-0502 (ISSN-L)
- 1549-5485
- PMC
- PMC3578275
- OpenAlex
- W2110140381
- Cited by
- 41
- References
- 55
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 2 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 4
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Learning & Memory (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH081004, MH081004)
- National Institute on Drug Abuse (R00DA023700, K99DA023700, DA023700)
- National Institute of Neurological Disorders and Stroke (R01NS078434, NS078434)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- hippocampal CA1, object location memory, allatostatin, inhibitory interneurons, memory formation, Cre-loxP system
- MeSH terms
- Animals, Catheterization, Interneurons, Ligands, Memory, Mice, Inbred C57BL, Mice, Transgenic, Nerve Net, Orientation, Pyramidal Cells, Receptors, Neuropeptide, Recognition, Psychology, Mice, CA1 Region, Hippocampal
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