While the above description focuses on the DG, it is worth considering how this resolution

may affect memory encoding within the CA3. It is important to note that the same CA3 neurons will receive inputs from a combination of both mature and immature neurons. While the potency of mossy fibers from immature GCs on CA3 is not fully understood (Toni et al., 2008), Dactolisib one possibility is that CA3 pyramidal neurons can only respond to single GCs if they are high information, and in contrast combinations of multiple active low information GCs may be required to induce CA3 activity. According to most classic hippocampal models, the active CA3 population, which only contains those neurons that receive inputs from informative mature GCs or groups of immature GCs, would then become bound to each other (through recurrent CA3 connections) and the direct EC inputs (Marr, 1971 and Treves and Rolls, 1992). Thus, when the “memory” is formed in CA3, rather than acting as an unsupervised training signal (i.e., random DG neurons active), the DG would provide a supervised cue based on the animal’s life experience up to that point. In summary, the memory

resolution hypothesis predicts that immature GCs provide a low-specificity yet densely sampled representation of cortical inputs, whereas mature GCs provide a highly specific yet sparse representation of an MK-2206 clinical trial event. This combined representation maximizes the information encoded by hippocampal memories, all thus increasing the memory’s resolution (behavioral discrimination), while keeping the memories formed distinct and minimizing interference in downstream attractor networks (computational pattern separation). Memories consisting of more familiar features would be expected to rely disproportionately on the mature population and thus have a particularly high resolution and a relative insensitivity to the presence of young neurons. In contrast, adult neurogenesis is particularly important for the resolution of memories of

particularly novel events since novel events would likely utilize fewer mature neurons. Notably, this mix between a mature neuron population optimally set up to respond to past experiences and a population of immature neurons with a capability to encode unforeseen events is reminiscent of the adaptive immune system where B and T cells are capable of responding to a novel infection by using naive cells that must develop the ability to fight antigens, whereas memory B and memory T cells can facilitate a rapid immunological response to address re-exposure to a past infection. According to the memory resolution hypothesis, it is conceivable that damage to the DG or neurogenesis would affect the quality of the formed memory, which can only be detected when the behavioral task requires high memory precision.