期刊
JOURNAL OF NEUROSCIENCE
卷 34, 期 14, 页码 5044-5053出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.5298-13.2014
关键词
awake mouse; depression; hippocampus; motivation; operant conditioning; synaptic activity
资金
- Japan Society for the Promotion of Science through the Funding Program for Next Generation World-Leading Researchers (NEXT Program) [22115003, 23115101, 25119004]
- Council for Science and Technology Policy [LS023]
- Strategic Research Program for Brain Sciences
- Grants-in-Aid for Scientific Research [25119004, 11J10930] Funding Source: KAKEN
Learning is a process of plastic adaptation through which a neural circuit generates a more preferable outcome; however, at a microscopic level, little is known about how synaptic activity is patterned into a desired configuration. Here, we report that animals can generate a specific form of synaptic activity in a given neuron in the hippocampus. In awake, head-restricted mice, we applied electrical stimulation to the lateral hypothalamus, a reward-associated brain region, when whole-cell patch-clamped CA1 neurons exhibited spontaneous synaptic activity that met preset criteria. Within 15 min, the mice learned to generate frequently the excitatory synaptic input pattern that satisfied the criteria. This reinforcement learning of synaptic activity was not observed for inhibitory input patterns. When a burst unit activity pattern was conditioned in paired and nonpaired paradigms, the frequency of burst-spiking events increased and decreased, respectively. The burst reinforcement occurred in the conditioned neuron but not in other adjacent neurons; however, ripple field oscillations were concomitantly reinforced. Neural conditioning depended on activation of NMDA receptors and dopamine D-1 receptors. Acutely stressed mice and depression model mice that were subjected to forced swimming failed to exhibit the neural conditioning. This learning deficit was rescued by repetitive treatment with fluoxetine, an antidepressant. Therefore, internally motivated animals are capable of routing an ongoing action potential series into a specific neural pathway of the hippocampal network.
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