Safe subdural administration and retention of a neurotrophin-3-delivering hydrogel in a rat model of spinal cord injury.

Neurotrophic growth factor (GF) loaded hydrogels have shown promise as a treatment approach for spinal cord injury (SCI). However, SCI presents complex challenges for the direct administration of treatment due to the spinal cord's intricate anatomy and highly sensitive environment. Many current hydrogel administration approaches overlook this complexity, limiting their translational potential.

Encapsulation of the growth factor neurotrophin-3 in heparinised poloxamer hydrogel stabilises bioactivity and provides sustained release.

Poloxamer-based hydrogels show promise to stabilise and sustain the delivery of growth factors in tissue engineering applications, such as following spinal cord injury. Typically, growth factors such as neurotrophin-3 (NT-3) degrade rapidly in solution. Similarly, poloxamer hydrogels also degrade readily and are, therefore, only capable of sustaining the release of a payload over a small number of days.

Translating ultrasound-mediated drug delivery technologies for CNS applications.

Ultrasound enhances drug delivery into the central nervous system (CNS) by opening barriers between the blood and CNS and by triggering release of drugs from carriers. A key challenge in translating setups from in vitro to in vivo settings is achieving equivalent acoustic energy delivery. Multiple devices have now been demonstrated to focus ultrasound to the brain, with concepts emerging to also target the spinal cord.

Generation of direct current electrical fields as regenerative therapy for spinal cord injury: A review.

Electrical stimulation (ES) shows promise as a therapy to promote recovery and regeneration after spinal cord injury. ES therapy establishes beneficial electric fields (EFs) and has been investigated in numerous studies, which date back nearly a century. In this review, we discuss the various engineering approaches available to generate regenerative EFs through direct current electrical stimulation and very low frequency electrical stimulation.

Neuron arbor geometry is sensitive to the limited-range fractal properties of their dendrites.

Fractal geometry is a well-known model for capturing the multi-scaled complexity of many natural objects. By analyzing three-dimensional images of pyramidal neurons in the rat hippocampus CA1 region, we examine how the individual dendrites within the neuron arbor relate to the fractal properties of the arbor as a whole. We find that the dendrites reveal unexpectedly mild fractal characteristics quantified by a low fractal dimension.

Investigating the influence of ultrasound parameters on ibuprofen drug release from hydrogels.

Hydrogels are promising ultrasound-responsive drug delivery systems. In this study, we investigated how different ultrasound parameters affected drug release and structural integrity of self-healing hydrogels composed of alginate or poloxamers. The effects of amplitude and duty cycle at low frequency (24 kHz) ultrasound stimulation were first investigated using alginate hydrogels at 2% w/v and 2.

Investigating Fractal Analysis as a Diagnostic Tool That Probes the Connectivity of Hippocampal Neurons.

Many of nature's fractal objects benefit from the favorable functionality that results from their pattern repetition at multiple scales. Our recent research focused on the importance of fractal scaling in establishing connectivity between neurons. Fractal dimension of the neuron arbors was shown to relate to the optimization of competing functional constraints-the ability of dendrites to connect to other neurons versus the costs associated with building the dendrites.

A Subdural Bioelectronic Implant to Record Electrical Activity from the Spinal Cord in Freely Moving Rats.

Bioelectronic devices have found use at the interface with neural tissue to investigate and treat nervous system disorders. Here, the development and characterization of a very thin flexible bioelectronic implant inserted along the thoracic spinal cord in rats directly in contact with and conformable to the dorsal surface of the spinal cord are presented. There is no negative impact on hind-limb functionality nor any change in the volume or shape of the spinal cord.

Dorsal CA1 hippocampal place cells form a multi-scale representation of megaspace.

Spatially firing "place cells" within the hippocampal CA1 region form internal maps of the environment necessary for navigation and memory. In rodents, these neurons have been almost exclusively studied in small environments (<4 m). It remains unclear how place cells encode a very large open 2D environment that is commensurate with the natural environments experienced by rodents and other mammals.

Enriched Environment Procedures for Rodents: Creating a Standardized Protocol for Diverse Enrichment to Improve Consistency across Research Studies.

Exposure to environmental enrichment has beneficial effects on learning and memory, diverse neurobiological effects, and promotes recovery of function after brain injury. The effect of enrichment is produced by a combination of increased social interaction, physical activity, spatial complexity, and novelty. Procedures in the literature have, however, been idiosyncratic with poor consistency in the manner or extent to which protocols provide consistent enrichment.

Interoceptive Insular Cortex Mediates Both Innate Fear and Contextual Threat Conditioning to Predator Odor.

The insular cortex (IC), among other brain regions, becomes active when humans experience fear or anxiety. However, few experimental studies in rats have implicated the IC in threat responses. We have recently reported that inactivation of the primary interoceptive cortex (pIC) during pre-training, or the intra-pIC blockade of protein synthesis immediately after training, impaired the consolidation of auditory fear conditioning.

Reservoir computing model of prefrontal cortex creates novel combinations of previous navigation sequences from hippocampal place-cell replay with spatial reward propagation.

As rats learn to search for multiple sources of food or water in a complex environment, they generate increasingly efficient trajectories between reward sites. Such spatial navigation capacity involves the replay of hippocampal place-cells during awake states, generating small sequences of spatially related place-cell activity that we call "snippets". These snippets occur primarily during sharp-wave-ripples (SWRs).

A new rat-compatible robotic framework for spatial navigation behavioral experiments.

Background: Understanding the neural substrate of information encoding and processing requires a precise control of the animal's behavior. Most of what has been learned from the rodent navigational system results from relatively simple tasks in which the movements of the animal is controlled by corridors or walkways, passive movements, treadmills or virtual reality environments. While a lot has been and continues to be learned from these types of experiments, recent evidence has shown that such artificial constraints may have significant consequences on the functioning of the neural circuits of spatial navigation.

Lesions of the Head Direction Cell System Increase Hippocampal Place Field Repetition.

A central tenet of systems neuroscience is that the mammalian hippocampus provides a cognitive map of the environment. This view is supported by the finding of place cells, neurons whose firing is tuned to specific locations in an animal's environment, within this brain region. Recent work, however, has shown that these cells repeat their firing fields across visually identical maze compartments [1, 2].

The head direction cell system and behavior: The effects of lesions to the lateral mammillary bodies on spatial memory in a novel landmark task and in the water maze.

The head direction system is composed of neurons found in a number of connected brain areas that fire in a sharply tuned, directional way. The function of this system, however, has not been fully established. To assess this, we devised a novel spatial landmark task, comparable to the paradigms in which stimulus control has been assessed for spatially tuned neurons.

Place field repetition and spatial learning in a multicompartment environment.

Recent studies have shown that place cells in the hippocampus possess firing fields that repeat in physically similar, parallel environments. These results imply that it should be difficult for animals to distinguish parallel environments at a behavioral level. To test this, we trained rats on a novel odor-location task in an environment with four parallel compartments which had previously been shown to yield place field repetition.

Anterior thalamic nuclei lesions and recovery of function: Relevance to cognitive thalamus.

Injury to the anterior thalamic nuclei (ATN) and their neural connections is the most consistent neuropathology associated with diencephalic amnesia. ATN lesions in rats produce memory impairments that support a key role for this region within an extended hippocampal system of complex overlapping neural connections. Environmental enrichment is a therapeutic tool that produces substantial, although incomplete, recovery of memory function after ATN lesions, even after the lesion-induced deficit has become established.

Anterior thalamic lesions reduce spine density in both hippocampal CA1 and retrosplenial cortex, but enrichment rescues CA1 spines only.

Injury to the anterior thalamic nuclei (ATN) may affect both hippocampus and retrosplenial cortex thus explaining some parallels between diencephalic and medial temporal lobe amnesias. We found that standard-housed rats with ATN lesions, compared with standard-housed controls, showed reduced spine density in hippocampal CA1 neurons (basal dendrites, -11.2%; apical dendrites, -9.