Chiaki I Santiago

• Bachelor of Arts
• University of California, San Diego

Clinical and translational studies suggest that prefrontal cortex (PFC) dysregulation is a hallmark feature of several affective disorders. Thus, investigating the mechanisms involved in the regulation of PFC function and synaptic plasticity could aid in developing new medications. In recent years, the mGlu2 and mGlu3 subtypes of metabotropic gluta...

Non-selective antagonists of metabotropic glutamate receptor subtypes 2 (mGlu2) and 3 (mGlu3) exert rapid antidepressant-like effects by enhancing prefrontal cortex (PFC) glutamate transmission; however, the receptor subtype contributions and underlying mechanisms remain unclear. Here, we leveraged newly developed negative allosteric modulators (NA...

Stress can precipitate or worsen symptoms of many psychiatric disorders by dysregulating glutamatergic function within the prefrontal cortex (PFC). Previous studies suggest that antagonists of group II metabotropic glutamate (mGlu) receptors (mGlu2 and mGlu3) reduce stress-induced anhedonia through actions in the PFC, but the mechanisms by which th...

Stress can precipitate or worsen symptoms of many psychiatric illnesses. Dysregulation of the prefrontal cortex (PFC) glutamate system may underlie these disruptions and restoring PFC glutamate signaling has emerged as a promising avenue for the treatment of stress disorders. Recently, we demonstrated that activation of metabotropic glutamate recep...

Introduction Current first‐line medications for Major depressive disorder (MDD) exhibit an undesirable delay in onset and poor efficacy in the general population, and there remains a great unmet need for novel fast‐acting antidepressant medications that retain efficacy in treatment‐resistant populations. The rapid reversal of depressive‐like sympto...

Figure S3. Immediate and long-term decreases in sEPSC amplitude and frequency during induction of mGlu3-LTD. (a) mGlu3-LTD coincides with sustained decrease in sEPSC amplitude (*: p < 0.05, Bonferonni post-test, n/N = 16/13 cells/mice). (b) mGlu3-LTD coincides with sustained decrease in sEPSC frequency (**: p < 0.01, Bonferonni post-test, n/N = 16/...

Figure S6. Diagram displaying hypothesized changes to BLA-PFC mGlu3-LTD following acute stress exposure. (Left) In PFC pyramidal cells, activation of mGlu3 generates LTD through a postsynaptic mechanism, consistent with the rapid AMPAR internalization and a decrease in the number of active synapses. This LTD occurs at inputs from the BLA and not fr...

Figure S2. Transient depression is mediated by mGlu2. Both the transient and long-term depression of excitatory transmission induced by LY379268 are blocked by the mGlu2/3 antagonist, LY341495 (95 ± 10 % baseline, n/N = 4/3 cells/mice). EPSC, excitatory postsynaptic current; mGlu2/3, metabotropic glutamate receptor subtypes 2 and 3.

Figure S5. Posttreatment with VU0650786 rescues stress-induced deficits to BLA-PFC mGlu3-LTD. (a) Schematic displaying stress exposure paradigm. Mice were treated with i.p. injections of the mGlu3 NAM VU0650786 immediately following immobilization stress. Slices were prepared for electrophysiology 30 minutes later. (b) BLA-PFC LTD remained intact i...

Figure S1. Group II mGlu activation does not alter inhibitory transmission in the PFC. (a) Representative traces and experiment. IPSCs were recorded with a high-chloride internal solution at −70 mV in the presence of CNQX. Scale bars denote 200 pA and 50 ms. (b) Summary timecourse of IPSC recordings during and after bath application of LY379268 (91...

Figure S4. Timecourse of stress-induced impairment in PFC mGlu3-LTD. (a) Summary time course of long-term recordings the day after acute stress exposure. LTD was impaired one day following acute stress (84 ± 9 % baseline, n/N = 5/3 cells/mice). (b) Summary time course of LTD recordings three days after acute stress exposure. LTD was not different f...