Expression of type I mGluRs predicts plasticity in the hippocampal stratum radiatum interneurons

Abstract

Changes in synaptic strength between hippocampal CA1 pyramidal cell synapses are partly responsible for memory acquisition. This plasticity is modulated by feedforward inhibitory interneurons in the stratum radiatum. While radiatum interneurons experience either long-term depression (LTD), short-term depression (STD), or lack plasticity, it is unclear whether plasticity correlates to specific interneuron subtypes. Using whole-cell electrophysiology and real-time quantitative PCR, we characterized the plasticity expressed by different interneuron subtypes. We first analyzed calcium binding proteins and cholecystokinin mRNA expression patterns to determine cell subtype. We then assessed endocannabinoid (eCB) biosynthetic enzyme mRNA expression, including diacylglycerol lipase α, N-acyl-phosphatidylethanolamine phospholipase D, and 12-lipoxygenase, and metabotropic glutamate receptors that often mediate plasticity. Neurons exhibiting LTD tended to co-express mRNA for at least one eCB biosynthetic enzyme and the metabotropic glutamate receptor 5 (mGluR5). Conversely, mGluR5 was not expressed by neurons exhibiting STD or no plasticity. Neurons that exhibited STD tended to express mRNA for at least one eCB biosynthetic enzyme and mGluR1, but not mGluR5. This suggests that plasticity of stratum radiatum interneurons could be predicted based on type I mGluR expression.

Keywords: 12-LO; DAGLα; Hippocampus; LTD; NAPE-PLD; Synaptic plasticity; mGluR1; mGluR5.

Figure 1:

Plasticity Profiles of Stratum Radiatum Interneurons. A. 50% of cells displayed long-term depression (LTD) of evoked glutamatergic excitatory postsynaptic currents (EPSCs) in whole cell voltage clamp mode (n = 13, p<0.05 between baseline and 10-20 minutes post-conditioning). B. In addition, 37% of interneurons expressed short term depression (STD) which returned to baseline approximately 10-15 minutes post-conditioning (n = 10; p< 0.05 between 0-10 minutes post-conditioning compared to baseline; p>0.05 at 15+ minutes post-conditioning). C. Lastly, approximately 14% of cells studied displayed no plasticity (n = 4; p>0.05 at all time points). ANOVA was used for quantification and to categorize types. Scale bars: 10ms, 100pA. Data represent means ± SEM.

Figure 2:

Gene expression profiles of stratum radiatum interneurons. A. The quantitative PCR (qPCR) of an example cell from figure 1A that demonstrated LTD. These cells always expressed mRNA for at least one eCB biosynthetic enzyme and most often for type I metabotropic glutamate receptors (mGluRs), especially mGluR5. B. An example cell from figure 1B that demonstrated STD. These cells often expressed mRNA for eCB biosynthetic enzymes and also for mGluR1. C. An example of one cell that did not exhibit plasticity from figure 1C. While a few of these neurons express mRNA for eCB biosynthetic enzymes (see Table 2), none expressed type I mGluRs. Data are represented as log-scaled relative fluorescence curves from FAM-TAMRA probe-based qPCR.