| First Author | Damborsky JC | Year | 2024 |
| Journal | J Mol Neurosci | Volume | 74 |
| Issue | 3 | Pages | 82 |
| PubMed ID | 39212758 | Mgi Jnum | J:359065 |
| Mgi Id | MGI:7782761 | Doi | 10.1007/s12031-024-02260-0 |
| Citation | Damborsky JC, et al. (2024) Regulation of Hippocamposeptal Synaptic Transmission by GABA(B)Rs Is Altered in 5XFAD Mice in a Sex- and Age-Dependent Manner. J Mol Neurosci 74(3):82 |
| abstractText | Hippocamposeptal (HS) neurons send GABAergic projections from the hippocampus to the medial septum/diagonal band of Broca (MS/DBB) as part of a reciprocal loop that is critical for memory. HS neurons are proposed to be particularly sensitive to the deleterious effects of pathological exposure to amyloid-beta (Abeta), as would occur during Alzheimer's disease (AD). However, it is not known how HS GABA release in the MS/DBB is altered during the progression of AD. To target HS neurons in a mouse model of AD, we crossed SST-Cre mice to 5XFAD mice and performed stereotaxic injections of Cre-dependent AAV containing mCherry/channelrhodopsin-2 (ChR2) into the hippocampus of offspring at 4, 6, 9, and 12 months. We used optogenetics to selectively stimulate HS terminals while performing whole-cell patch-clamp recordings from MS/DBB neurons in slices. There was a transient reduction in HS-inhibitory postsynaptic current (IPSC) amplitude in female 5XFAD mice at 6 months, but no difference in males at any age, and no difference in paired-pulse ratio in either sex at any age. When bath applying the GABA(B)R agonist, baclofen, we found a larger decrease in HS-IPSC amplitude in 5XFAD females at 9 months and 5XFAD males at 12 months. In 12-month-old 5XFAD females, response to baclofen was significantly reduced. These data suggest that there is a transient increase in responsiveness to GABA(B)R activation in 5XFAD mice that occurs earlier in females than in males. These sex-specific changes to HS function are likely to impact the relay of information between the hippocampus and MS/DBB. |
