Astrocyte and L-lactate in the anterior cingulate cortex modulate schema memory and neuronal mitochondrial biogenesis

Area of Science:

• Neuroscience
• Cellular Neuroscience
• Cognitive Neuroscience

Background:

• Astrocyte-derived L-lactate supports synaptic plasticity and cognitive functions.
• The role of astrocytic G_i signaling in the anterior cingulate cortex (ACC) on L-lactate levels and schema memory remains unclear.

Purpose of the Study:

• To investigate how astrocytic G_i signaling in the ACC influences L-lactate levels, schema memory, and related cognitive functions.
• To elucidate the underlying mechanisms connecting astrocytic G_i signaling, L-lactate, and memory formation.

Main Methods:

• Chemogenetic manipulation of astrocytic G_i signaling in the ACC of rats.
• Behavioral paradigms assessing paired associates (PA) learning, schema formation, and memory retrieval.
• Measurement of L-lactate levels and assessment of neuronal mitochondrial biogenesis.

Main Results:

• Activation of astrocytic G_i pathway in the ACC significantly impaired PA learning, schema formation, and memory retrieval.
• These impairments were linked to decreased L-lactate levels in the ACC, which were rescued by exogenous L-lactate administration.
• Impaired schema memory correlated with reduced neuronal mitochondrial biogenesis, dependent on L-lactate, monocarboxylate transporter 2 (MCT2), and NMDA receptor activity.

Conclusions:

• Astrocytic G_i signaling in the ACC negatively regulates L-lactate levels, impacting schema memory and cognitive functions.
• L-lactate plays a critical role in neuronal mitochondrial biogenesis and memory, mediated by MCT2 and NMDA receptors.
• This study reveals a novel signaling pathway involving astrocytes, L-lactate, and mitochondrial function in brain memory processes.