Early life events have profound consequences. Our research demonstrates that the early life stress of neonatal isolation (1-h individual isolation on postnatal days 2-9) in rats has immediate and enduring neural and behavioral effects. Recently, we showed neonatal isolation impaired hippocampal-dependent context conditioned fear in adult rats. We now expand upon this finding to test whether neonatal isolation impairs performance in inhibitory avoidance and in the non-aversive, hippocampal-dependent object recognition task. In addition to assessments of hippocampal-dependent memory, we examined if neonatal isolation results in cellular alterations in the adult hippocampus. This was measured with antibodies that selectively label calpain-mediated spectrin breakdown product (BDP), a marker of cytoskeletal modification that can have neuronal consequences. Neonatally isolated male and female rats showed impaired performance in both memory tasks as well as elevated BDP levels in hippocampal immunoblot samples. In tissue sections stained for BDP, the cytoskeletal fragmentation was localized to pyramidal neurons and their proximal dendrites. Interestingly, the hippocampal samples also exhibited reduced staining for the postsynaptic marker, GluR1. Neonatal isolation may render those neurons involved in memory encoding to be vulnerable to calpain deregulation and synaptic compromise as shown previously with brain injury. Together with our prior research showing enhanced striatal-dependent learning and neurochemical responsivity, these results indicate that the early experience of neonatal isolation causes enduring yet opposing region-specific neural and behavioral alterations.