A Possible Mechanism for Development of Working Memory Impairment in Male Mice Subjected to Inflammatory Pain

Overview

Journal Neuroscience

Specialty Neurology

Date 2022 Sep 13

PMID 36100034

Authors

Alexander Papadogiannis

Eugene Dimitrov

Affiliations

Soon will be listed here.

Abstract

We studied the effects of inflammatory pain on working memory and correlated the pain effects with changes in dendritic spine density and glutamate signaling in the medial prefrontal cortex (mPFC) of male and female mice. Injection of Complete Freund's Adjuvant (CFA) into the hind paw modeled inflammatory pain. The CFA equally decreased the mechanical thresholds in both sexes. The density of dendritic spines, as a marker for neuronal input, increased on the dendrites of both, pyramidal cells and interneurons in males but only on the dendrites of interneurons in CFA injected females. Next, we injected virus with glutamate sensor (pAAV.hSyn.iGluSnFr) into the mPFC and used fiber photometry to record glutamate signaling during Y-maze spontaneous alternations test, which is a test for working memory in rodents. The detected fluorescent signal was higher during correct alternations when compared to incorrect alternations in both sexes. The CFA injection did not change the pattern of glutamate fluorescence during the test but the female mice made fewer incorrect alternations than their male counterparts. Furthermore, while the CFA injection decreased the expression of the glutamate transporter VGlut1 on the soma of mPFC neurons in both sexes, the decrease was sex dependent. We concluded that inflammatory pain, which increases sensory input into the mPFC neurons, may impair working memory by altering the glutamate signaling. The glutamate deficit that develops as a result of the pain is more pronounced in male mice in comparison to female mice.

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References

Latremoliere A, Woolf C . Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009; 10(9):895-926. PMC: 2750819. DOI: 10.1016/j.jpain.2009.06.012. View

Kraeuter A, Guest P, Sarnyai Z . The Y-Maze for Assessment of Spatial Working and Reference Memory in Mice. Methods Mol Biol. 2018; 1916:105-111. DOI: 10.1007/978-1-4939-8994-2_10. View

Bruno C, OBrien C, Bryant S, Mejaes J, Estrin D, Pizzano C . pMAT: An open-source software suite for the analysis of fiber photometry data. Pharmacol Biochem Behav. 2021; 201:173093. PMC: 7853640. DOI: 10.1016/j.pbb.2020.173093. View

Stratton H, Khanna R . Sculpting Dendritic Spines during Initiation and Maintenance of Neuropathic Pain. J Neurosci. 2020; 40(40):7578-7589. PMC: 7531544. DOI: 10.1523/JNEUROSCI.1664-20.2020. View

Wu X, Liang B, Gao Y . The increase of intrinsic excitability of layer V pyramidal cells in the prelimbic medial prefrontal cortex of adult mice after peripheral inflammation. Neurosci Lett. 2015; 611:40-5. DOI: 10.1016/j.neulet.2015.11.030. View

Tan L, Oswald M, Heinl C, Retana Romero O, Kaushalya S, Monyer H . Gamma oscillations in somatosensory cortex recruit prefrontal and descending serotonergic pathways in aversion and nociception. Nat Commun. 2019; 10(1):983. PMC: 6395755. DOI: 10.1038/s41467-019-08873-z. View

Ren K, Dubner R . Inflammatory Models of Pain and Hyperalgesia. ILAR J. 2001; 40(3):111-118. DOI: 10.1093/ilar.40.3.111. View

Bastos A, Loonis R, Kornblith S, Lundqvist M, Miller E . Laminar recordings in frontal cortex suggest distinct layers for maintenance and control of working memory. Proc Natl Acad Sci U S A. 2018; 115(5):1117-1122. PMC: 5798320. DOI: 10.1073/pnas.1710323115. View

Hung K, Wang S, Wang Y, Chiang T, Wang C . Upregulation of presynaptic proteins and protein kinases associated with enhanced glutamate release from axonal terminals (synaptosomes) of the medial prefrontal cortex in rats with neuropathic pain. Pain. 2013; 155(2):377-387. DOI: 10.1016/j.pain.2013.10.026. View

10.

Laubach M, Amarante L, Swanson K, White S . What, If Anything, Is Rodent Prefrontal Cortex?. eNeuro. 2018; 5(5). PMC: 6220587. DOI: 10.1523/ENEURO.0315-18.2018. View

11.

Van De Werd H, Rajkowska G, Evers P, Uylings H . Cytoarchitectonic and chemoarchitectonic characterization of the prefrontal cortical areas in the mouse. Brain Struct Funct. 2010; 214(4):339-53. PMC: 2862954. DOI: 10.1007/s00429-010-0247-z. View

12.

Giordano C, Cristino L, Luongo L, Siniscalco D, Petrosino S, Piscitelli F . TRPV1-dependent and -independent alterations in the limbic cortex of neuropathic mice: impact on glial caspases and pain perception. Cereb Cortex. 2011; 22(11):2495-518. PMC: 3464411. DOI: 10.1093/cercor/bhr328. View

13.

Jefferson T, Kelly C, Martina M . Differential Rearrangement of Excitatory Inputs to the Medial Prefrontal Cortex in Chronic Pain Models. Front Neural Circuits. 2022; 15:791043. PMC: 8738091. DOI: 10.3389/fncir.2021.791043. View

14.

Mazza S, Frot M, Rey A . A comprehensive literature review of chronic pain and memory. Prog Neuropsychopharmacol Biol Psychiatry. 2017; 87(Pt B):183-192. DOI: 10.1016/j.pnpbp.2017.08.006. View

15.

DIXON W . Staircase bioassay: the up-and-down method. Neurosci Biobehav Rev. 1991; 15(1):47-50. DOI: 10.1016/s0149-7634(05)80090-9. View

16.

Euston D, Gruber A, McNaughton B . The role of medial prefrontal cortex in memory and decision making. Neuron. 2012; 76(6):1057-70. PMC: 3562704. DOI: 10.1016/j.neuron.2012.12.002. View

17.

van Asselen M, Kessels R, Neggers S, Kappelle L, Frijns C, Postma A . Brain areas involved in spatial working memory. Neuropsychologia. 2005; 44(7):1185-94. DOI: 10.1016/j.neuropsychologia.2005.10.005. View

18.

Tyrtyshnaia A, Manzhulo I . Neuropathic Pain Causes Memory Deficits and Dendrite Tree Morphology Changes in Mouse Hippocampus. J Pain Res. 2020; 13:345-354. PMC: 7023911. DOI: 10.2147/JPR.S238458. View

19.

Naylor B, Hesam-Shariati N, McAuley J, Boag S, Newton-John T, Rae C . Reduced Glutamate in the Medial Prefrontal Cortex Is Associated With Emotional and Cognitive Dysregulation in People With Chronic Pain. Front Neurol. 2019; 10:1110. PMC: 6903775. DOI: 10.3389/fneur.2019.01110. View

20.

Tian Y, Yang C, Cui Y, Su F, Wang Y, Wang Y . An Excitatory Neural Assembly Encodes Short-Term Memory in the Prefrontal Cortex. Cell Rep. 2018; 22(7):1734-1744. DOI: 10.1016/j.celrep.2018.01.050. View