Glutamate-specific gene linked to human brain evolution enhances synaptic plasticity and cognitive processes.

ABSTRACT: The human brain is characterized by the upregulation of synaptic, mainly glutamatergic, transmission, but its evolutionary origin(s) remain elusive. Here we approached this fundamental question by studying mice transgenic (Tg) for GLUD2, a human gene involved in glutamate metabolism that emerged in the hominoid and evolved concomitantly with brain expansion. We demonstrate that Tg mice express the human enzyme in hippocampal astrocytes and CA1-CA3 pyramidal neurons. LTP, evoked by theta-burst stimulation, is markedly enhanced in the CA3-CA1 synapses of Tg mice, with patch-clamp recordings from CA1 pyramidal neurons revealing increased sNMDA currents. LTP enhancement is blocked by D-lactate, implying that GLUD2 potentiates L-lactate-mediated astrocyte-neuron interaction. Dendr

SUBMITTER: Spanaki C 

PROVIDER: S-EPMC10850756 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature