Supramammillary nucleus synchronizes with dentate gyrus to regulate spatial memory retrieval through glutamate...

Area of Science:

• Neuroscience
• Systems Neuroscience
• Cognitive Neuroscience

Background:

• The supramammillary nucleus (SuM) extensively innervates the dentate gyrus (DG), a key region for spatial memory.
• The circuit-level coordination between SuM and DG and the specific roles of SuM's co-released neurotransmitters (GABA and glutamate) in spatial memory remain unclear.

Purpose of the Study:

• To investigate the circuit dynamics between the SuM and DG during spatial memory encoding and retrieval.
• To determine the necessity of SuM neuronal activity and SuM-DG projections for spatial memory.
• To elucidate the distinct roles of GABAergic versus glutamatergic transmission from SuM to DG in spatial memory regulation.

Main Methods:

• Utilized calcium (Ca2+) imaging in mice performing a location discrimination task to assess SuM-DG activity correlations during encoding and retrieval.
• Employed optogenetic or chemogenetic techniques to manipulate SuM neuron or SuM-DG projection activity.
• Investigated the impact of selectively inhibiting SuM glutamate transmission on spatial memory and circuit activity.

Main Results:

• SuM-DG Ca2+ activities exhibited significantly higher correlations during spatial memory retrieval compared to memory encoding.
• Disruption of SuM neuron or SuM-DG projection activity impaired spatial memory retrieval.
• Inhibition of SuM glutamate transmission abolished spatial memory retrieval and the high SuM-DG activity correlation during retrieval.

Conclusions:

• A long-range circuit connecting the SuM and DG is identified as critical for spatial memory retrieval.
• SuM glutamate release, not GABA, is essential for coordinating SuM-DG activity and enabling spatial memory retrieval.
• This study highlights the role of glutamatergic SuM-DG projections in linking subcortical regions for spatial memory function.