Training-induced circuit-specific excitatory synaptogenesis in mice is required for effort control.

Synaptogenesis is essential for circuit development; however, it is unknown whether it is critical for the establishment and performance of goal-directed voluntary behaviors. Here, we show that operant conditioning via lever-press for food reward training in mice induces excitatory synapse formation onto a subset of anterior cingulate cortex neurons projecting to the dorsomedial striatum (ACC→DMS). Training-induced synaptogenesis is controlled by the Gabapentin/Thrombospondin receptor α2δ-1, which is an essential neuronal protein for proper intracortical excitatory synaptogenesis. Using germline and conditional knockout mice, we found that deletion of α2δ-1 in the adult ACC→DMS circuit diminishes training-induced excitatory synaptogenesis. Surprisingly, this manipulation does not impact learning but results in a significant increase in effort exertion without affecting sensitivity to reward value or changing contingencies. Bidirectional optogenetic manipulation of ACC→DMS neurons rescues or phenocopies the behaviors of the α2δ-1 cKO mice, highlighting the importance of synaptogenesis within this cortico-striatal circuit in regulating effort exertion.

oVEMPs and cVEMPs in patients with 'clinically certain' Menière's disease.

OBJECTIVE: To measure ocular vestibular-evoked myogenic potentials (oVEMPs) and cervical vestibular-evoked myogenic potentials (cVEMPS) in Menière's disease patients with confirmed cochlear hydrops and in the normal ears of volunteers. METHODS: oVEMPs and cVEMPs were measured in 18 patients with a symptomatic diagnosis of Menière's disease and tone burst electrocochleographic confirmation of hydrops, and in the ears of 22 volunteers. RESULTS: Threshold measures: For cVEMP: no significant differences between Menière's ears and controls; for oVEMP: significantly elevated thresholds in affected ears of Menière's ears compared with their unaffected ears, but not with controls. Latency measures: cVEMP N1 peaks were significantly prolonged compared with the left and right ears of controls, but not with the non-affected ear. Amplitude measures: cVEMP P1N1 and N1P2 measures were significantly reduced compared with the right ear of controls, but not with the non-affected ear; For oVEMP, N2P2 amplitudes were significantly reduced compared with both ears of controls but not with the non-affected ear. CONCLUSION: Abnormalities of oVEMPs and cVEMPs were found in 18 Menière's disease patients who had an independent confirmation of cochlear hydrops. The overlap of the results from Menière's patients compared with normal controls limits the use of VEMP abnormalities as a sole reliable diagnostic test for Menière's disease.