Distinct neuronal populations contribute to trace conditioning and extinction learning in the hippocampal CA1.

Trace conditioning and extinction learning depend on the hippocampus, but it remains unclear how neural activity in the hippocampus is modulated during these two different behavioral processes. To explore this question, we performed calcium imaging from a large number of individual CA1 neurons during both trace eye-blink conditioning and subsequent extinction learning in mice. Our findings reveal that distinct populations of CA1 cells contribute to trace conditioned learning versus extinction learning, as learning emerges. Furthermore, we examined network connectivity by calculating co-activity between CA1 neuron pairs and found that CA1 network connectivity patterns also differ between conditioning and extinction, even though the overall connectivity density remains constant. Together, our results demonstrate that distinct populations of hippocampal CA1 neurons, forming different sub-networks with unique connectivity patterns, encode different aspects of learning.

Mild Blast Injury Produces Acute Changes in Basal Intracellular Calcium Levels and Activity Patterns in Mouse Hippocampal Neurons.

Mild traumatic brain injury (mTBI) represents a serious public health concern. Although much is understood about long-term changes in cell signaling and anatomical pathologies associated with mTBI, little is known about acute changes in neuronal function. Using large scale Ca2+ imaging in vivo, we characterized the intracellular Ca2+ dynamics in thousands of individual hippocampal neurons using a repetitive mild blast injury model in which blasts were directed onto the cranium of unanesthetized mice on two consecutive days. Immediately following each blast event, neurons exhibited two types of changes in Ca2+ dynamics at different time scales. One was a reduction in slow Ca2+ dynamics that corresponded to shifts in basal intracellular Ca2+ levels at a time scale of minutes, suggesting a disruption of biochemical signaling. The second was a reduction in the rates of fast transient Ca2+ fluctuations at the sub-second time scale, which are known to be closely linked to neural activity. Interestingly, the blast-induced changes in basal Ca2+ levels were independent of the changes in the rates of fast Ca2+ transients, suggesting that blasts had heterogeneous effects on different cell populations. Both types of changes recovered after ∼1 h. Together, our results demonstrate that mTBI induced acute, heterogeneous changes in neuronal function, altering intracellular Ca2+ dynamics across different time scales, which may contribute to the initiation of longer-term pathologies.