Cognitive control persistently enhances hippocampal information processing.

Could learning that uses cognitive control to judiciously use relevant information while ignoring distractions generally improve brain function, beyond forming explicit memories? According to a neuroplasticity hypothesis for how some cognitive behavioural therapies are effective, cognitive control training (CCT) changes neural circuit information processing1-3. Here we investigated whether CCT persistently alters hippocampal neural circuit function. We show that mice learned and remembered a conditioned place avoidance during CCT that required ignoring irrelevant locations of shock. CCT facilitated learning new tasks in novel environments for several weeks, relative to unconditioned controls and control mice that avoided the same place during reduced distraction. CCT rapidly changes entorhinal cortex-to-dentate gyrus synaptic circuit function, resulting in an excitatory-inhibitory subcircuit change that persists for months. CCT increases inhibition that attenuates the dentate response to medial entorhinal cortical input, and through disinhibition, potentiates the response to strong inputs, pointing to overall signal-to-noise enhancement. These neurobiological findings support the neuroplasticity hypothesis that, as well as storing item-event associations, CCT persistently optimizes neural circuit information processing.

Is hippocampal remapping the physiological basis for context?

In 1980, Nadel and Wilner extended Richard Hirsh's notion that the hippocampus creates environmental representations, called "contexts," suggesting that the fundamental structure of context was the spatial representation proposed by O'Keefe and Nadel's landmark book, The Hippocampus as a Cognitive Map (1978). This book, in turn, derives from the discovery that individual hippocampal neurons act as place cells, with the complete set of place cells tiling an enclosure, forming a type of spatial map. It was found that unique environments had unique place cell representations. That is, if one takes the hippocampal map of a specific environment, this representation scrambles, or "remaps" when the animal is placed in a different environment. Several authors have speculated that "maps" and "remapping" form the physiological substrates for context and context shifting. One difficulty with this definition is that it is exclusively spatial; it can only be inferred when an animal locomotes in an enclosure. There are five aims for this article. The first is to give an historical overview of context as a variable that controls behavior. The second aim is to give an historical overview of concepts of place cell maps and remapping. The third aim is to propose an updated definition of a place cell map, based on temporal rather than spatial overlaps, which adds flexibility. The fourth aim is to address the issue of whether the biological phenomenon of hippocampal remapping, is, in fact, the substrate for shifts in the psychological phenomenon of context. The final aim is speculation of how contextual representations may contribute to effective behavior.

Long-Lasting Input-Specific Experience-Dependent Changes of Hippocampus Synaptic Function Measured in the Anesthetized Rat.

How experience causes long-lasting changes in the brain is a central question in neuroscience. The common view is that synaptic function is altered by experience to change brain circuit functions that underlie conditioned behavior. We examined hippocampus synaptic circuit function in vivo, in three groups of animals, to assess the impact of experience on hippocampus function in rats. The "conditioned" group acquired a shock-conditioned place response during a cognitively-challenging, hippocampus synaptic plasticity-dependent task. The no-shock group had similar exposure to the environmental conditions but no conditioning. The home-cage group was experimentally naive. After the one-week retention test, under anesthesia, we stimulated the perforant path inputs to CA1, which terminate in stratum lacunosum moleculare (slm), and to the dentate gyrus (DG), which terminate in the molecular layer. We find synaptic compartment specific changes that differ amongst the groups. The evoked field EPSP (fEPSP) and pre-spike field response are enhanced only at the DG input layer and only in conditioned animals. The DG responses, measured by the population spiking activity and post-spike responses, are enhanced in both the conditioned and no-shock groups compared to home-cage animals. These changes are pathway specific because no differences are observed in slm of CA1. These findings demonstrate long-term, experience-dependent, pathway-specific alterations to synaptic circuit function of the hippocampus.

Sub-circuit alterations in dorsal hippocampus structure and function after global neurodevelopmental insult.

Patients with neuropsychiatric and neurological disorders often express limbic circuit abnormalities and deficits in information processing. While these disorders appear to have diverse etiologies, their common features suggest neurodevelopmental origins. Neurodevelopment is a prolonged process of diverse events including neurogenesis/apoptosis, axon pathfinding, synaptogenesis, and pruning, to name a few. The precise timing of the neurodevelopmental insult to these processes likely determines the resulting functional outcome. We used the epilepsy and schizophrenia-related gestational day 17 methylazoxymethanol acetate model to examine the impact of this timed neurodevelopmental insult on principal cell morphology and synaptic network function of the dorsal hippocampus (dHPC) circuit. Our observed structural and functional alterations in dHPC are compartment specific, indicating that adverse global exposure during gestation can produce specific alterations and distort information processing in neural circuits that underlie cognitive abilities.

Anisomorphic cortical reorganization in asymmetric sensorineural hearing loss.

Acoustic trauma or inner ear disease may predominantly injure one ear, causing asymmetric sensorineural hearing loss (SNHL). While characteristic frequency (CF) map plasticity of primary auditory cortex (AI) contralateral to the injured ear has been detailed, there is no study that also evaluates ipsilateral AI to compare cortical reorganization across both hemispheres. We assess whether the normal isomorphic mirror-image relationship between the two hemispheres is maintained or disrupted in mild-to-moderate asymmetric SNHL of adult squirrel monkeys. At week 24 after induction of acoustic injury to the right ear, functional organization of the two hemispheres differs in direction and magnitude of interaural CF difference, percentage of recording sites with spectrally nonoverlapping binaural activation, and the concurrence of peripheral and central activation thresholds. The emergence of this anisomorphic cortical reorganization of the two hemispheres is replicated by simulation based on spike timing-dependent plasticity, where 1) AI input from the contralateral ear is dominant, 2) reestablishment of relatively shorter contralateral ear input timing drives reorganization, and 3) only AI contralateral to the injured ear undergoes major realignment of interaural frequency maps that evolve over months. Asymmetric SNHL disrupts isomorphic organization between the two hemispheres and results in relative local hemispheric autonomy, potentially impairing performance of tasks that require binaural input alignment or interhemispheric processing.NEW & NOTEWORTHY Mild-to-moderate hearing loss in one ear and essentially normal hearing in the other triggers cortical reorganization that is different in the two hemispheres. Asymmetry of cochlea sensitivities does not simply propagate to the two auditory cortices in mirror-image fashion. The resulting anisomorphic cortical reorganization may be a neurophysiological basis of clinical deficits in asymmetric hearing loss, such as difficulty with hearing in noise, impaired spatial hearing, and accelerated decline of the poorer ear.