Disrupting direct inputs from the dorsal subiculum to the granular retrosplenial cortex impairs flexible spatial memory in the rat.

In a changing environment, animals must process spatial signals in a flexible manner. The rat hippocampal formation projects directly upon the retrosplenial cortex, with most inputs arising from the dorsal subiculum and terminating in the granular retrosplenial cortex (area 29). The present study examined whether these same projections are required for spatial working memory and what happens when available spatial cues are altered. Consequently, injections of iDREADDs were made into the dorsal subiculum of rats. In a separate control group, GFP-expressing adeno-associated virus was injected into the dorsal subiculum. Both groups received intracerebral infusions within the retrosplenial cortex of clozapine, which in the iDREADDs rats should selectively disrupt the subiculum to retrosplenial projections. When tested on reinforced T-maze alternation, disruption of the subiculum to retrosplenial projections had no evident effect on the performance of those alternation trials when all spatial-cue types remained present and unchanged. However, the same iDREADDs manipulation impaired performance on all three alternation conditions when there was a conflict or selective removal of spatial cues. These findings reveal how the direct projections from the dorsal subiculum to the retrosplenial cortex support the flexible integration of different spatial cue types, helping the animal to adopt the spatial strategy that best meets current environmental demands.

Anterior Thalamic Inputs Are Required for Subiculum Spatial Coding, with Associated Consequences for Hippocampal Spatial Memory.

Just as hippocampal lesions are principally responsible for "temporal lobe" amnesia, lesions affecting the anterior thalamic nuclei seem principally responsible for a similar loss of memory, "diencephalic" amnesia. Compared with the former, the causes of diencephalic amnesia have remained elusive. A potential clue comes from how the two sites are interconnected, as within the hippocampal formation, only the subiculum has direct, reciprocal connections with the anterior thalamic nuclei. We found that both permanent and reversible anterior thalamic nuclei lesions in male rats cause a cessation of subicular spatial signaling, reduce spatial memory performance to chance, but leave hippocampal CA1 place cells largely unaffected. We suggest that a core element of diencephalic amnesia stems from the information loss in hippocampal output regions following anterior thalamic pathology.SIGNIFICANCE STATEMENT At present, we know little about interactions between temporal lobe and diencephalic memory systems. Here, we focused on the subiculum, as the sole hippocampal formation region directly interconnected with the anterior thalamic nuclei. We combined reversible and permanent lesions of the anterior thalamic nuclei, electrophysiological recordings of the subiculum, and behavioral analyses. Our results were striking and clear: following permanent thalamic lesions, the diverse spatial signals normally found in the subiculum (including place cells, grid cells, and head-direction cells) all disappeared. Anterior thalamic lesions had no discernible impact on hippocampal CA1 place fields. Thus, spatial firing activity within the subiculum requires anterior thalamic function, as does successful spatial memory performance. Our findings provide a key missing part of the much bigger puzzle concerning why anterior thalamic damage is so catastrophic for spatial memory in rodents and episodic memory in humans.

Cell compaction is not required for the development of gradient refractive index profiles in the embryonic chick lens.

The development of the eye requires the co-ordinated integration of optical and neural elements to create a system with requisite optics for the given animal. The eye lens has a lamellar structure with gradually varying protein concentrations that increase towards the centre, creating a gradient refractive index or GRIN. This provides enhanced image quality compared to a homogeneous refractive index lens. The development of the GRIN during ocular embryogenesis has not been investigated previously. This study presents measurements using synchrotron X-ray Talbot interferometry and scanning electron microscopy of chick eyes from embryonic day 10: midway through embryonic development to E18: a few days before hatching. The lens GRIN profile is evident from the youngest age measured and increases in magnitude of refractive index at all points as the lens grows. The profile is parabolic along the optic axis and has two distinct regions in the equatorial plane. We postulate that these may be fundamental for the independent central and peripheral processes that contribute to the optimisation of image quality and the development of an eye that is emmetropic. The spatial distributions of the distinct GRIN profile regions match with previous measurements on different fibre cell groups in chick lenses of similar developmental stages. Results suggest that tissue compaction may not be necessary for development of the GRIN in the chick eye lens.

The Anatomical Boundary of the Rat Claustrum.

The claustrum is a subcortical nucleus that exhibits dense connectivity across the neocortex. Considerable recent progress has been made in establishing its genetic and anatomical characteristics, however, a core, contentious issue that regularly presents in the literature pertains to the rostral extent of its anatomical boundary. The present study addresses this issue in the rat brain. Using a combination of immunohistochemistry and neuroanatomical tract tracing, we have examined the expression profiles of several genes that have previously been identified as exhibiting a differential expression profile in the claustrum relative to the surrounding cortex. The expression profiles of parvalbumin (PV), crystallin mu (Crym), and guanine nucleotide binding protein (G protein), gamma 2 (Gng2) were assessed immunohistochemically alongside, or in combination with cortical anterograde, or retrograde tracer injections. Retrograde tracer injections into various thalamic nuclei were used to further establish the rostral border of the claustrum. Expression of all three markers delineated a nuclear boundary that extended considerably (∼500 µm) beyond the anterior horn of the neostriatum. Cortical retrograde and anterograde tracer injections, respectively, revealed distributions of cortically-projecting claustral neurons and cortical efferent inputs to the claustrum that overlapped with the gene marker-derived claustrum boundary. Finally, retrograde tracer injections into the thalamus revealed insular cortico-thalamic projections encapsulating a claustral area with strongly diminished cell label, that extended rostral to the striatum.

Mammillothalamic Disconnection Alters Hippocampocortical Oscillatory Activity and Microstructure: Implications for Diencephalic Amnesia.

Diencephalic amnesia can be as debilitating as the more commonly known temporal lobe amnesia, yet the precise contribution of diencephalic structures to memory processes remains elusive. Across four cohorts of male rats, we used discrete lesions of the mammillothalamic tract to model aspects of diencephalic amnesia and assessed the impact of these lesions on multiple measures of activity and plasticity within the hippocampus and retrosplenial cortex. Lesions of the mammillothalamic tract had widespread indirect effects on hippocampocortical oscillatory activity within both theta and gamma bands. Both within-region oscillatory activity and cross-regional synchrony were altered. The network changes were state-dependent, displaying different profiles during locomotion and paradoxical sleep. Consistent with the associations between oscillatory activity and plasticity, complementary analyses using several convergent approaches revealed microstructural changes, which appeared to reflect a suppression of learning-induced plasticity in lesioned animals. Together, these combined findings suggest a mechanism by which damage to the medial diencephalon can impact upon learning and memory processes, highlighting an important role for the mammillary bodies in the coordination of hippocampocortical activity.SIGNIFICANCE STATEMENT Information flow within the Papez circuit is critical to memory. Damage to ascending mammillothalamic projections has consistently been linked to amnesia in humans and spatial memory deficits in animal models. Here we report on the changes in hippocampocortical oscillatory dynamics that result from chronic lesions of the mammillothalamic tract and demonstrate, for the first time, that the mammillary bodies, independently of the supramammillary region, contribute to frequency modulation of hippocampocortical theta oscillations. Consistent with the associations between oscillatory activity and plasticity, the lesions also result in a suppression of learning-induced plasticity. Together, these data support new functional models whereby mammillary bodies are important for coordinating hippocampocortical activity rather than simply being a relay of hippocampal information as previously assumed.

The claustrum: Considerations regarding its anatomy, functions and a programme for research.

The claustrum is a highly conserved but enigmatic structure, with connections to the entire cortical mantle, as well as to an extended and extensive range of heterogeneous subcortical structures. Indeed, the human claustrum is thought to have the highest number of connections per millimetre cubed of any other brain region. While there have been relatively few functional investigations of the claustrum, many theoretical suggestions have been put forward, including speculation that it plays a key role in the generation of consciousness in the mammalian brain. Other claims have been more circumspect, suggesting that the claustrum has a particular role in, for example, orchestrating cortical activity, spatial information processing or decision making. Here, we selectively review certain key recent anatomical, electrophysiological and behavioural experimental advances in claustral research and present evidence that calls for a reassessment of its anatomical boundaries in the rodent. We conclude with some open questions for future research.