Geniculo-Cortical Projection Diversity Revealed within the Mouse Visual Thalamus.

The mouse dorsal lateral geniculate nucleus (dLGN) is an intermediary between retina and primary visual cortex (V1). Recent investigations are beginning to reveal regional complexity in mouse dLGN. Using local injections of retrograde tracers into V1 of adult and neonatal mice, we examined the developing organisation of geniculate projection columns: the population of dLGN-V1 projection neurons that converge in cortex. Serial sectioning of the dLGN enabled the distribution of labelled projection neurons to be reconstructed and collated within a common standardised space. This enabled us to determine: the organisation of cells within the dLGN-V1 projection columns; their internal organisation (topology); and their order relative to V1 (topography). Here, we report parameters of projection columns that are highly variable in young animals and refined in the adult, exhibiting profiles consistent with shell and core zones of the dLGN. Additionally, such profiles are disrupted in adult animals with reduced correlated spontaneous activity during development. Assessing the variability between groups with partial least squares regression suggests that 4-6 cryptic lamina may exist along the length of the projection column. Our findings further spotlight the diversity of the mouse dLGN--an increasingly important model system for understanding the pre-cortical organisation and processing of visual information. Furthermore, our approach of using standardised spaces and pooling information across many animals will enhance future functional studies of the dLGN.

An in vitro evaluation of selective demineralised enamel removal using bio-active glass air abrasion.

Unnecessary over-preparation of carious enamel often occurs clinically during operative caries management. The working hypothesis to be investigated in this study is the potential for bio-active glass air abrasion to remove selectively only demineralised enamel in artificial enamel lesions when compared to equivalent alumina air abrasion, so potentially minimising cavity over-preparation. Bisected artificial, paired smooth surface enamel lesions on ethics-approved, extracted sound human molars were created and subsequently air abraded with 27 µm alumina (n = 19) and bio-active glass (n = 19). The difference between pre-operative lesion boundary and post-operative cavity margin was calculated following optical confocal fluorescent assessment of the lesion boundary. Data indicated mean% over-preparation (sound enamel removal) of 176% with alumina and 15.2% for bio-active glass (p = 0.005). Bio-active glass abrasion removed completely the demineralised enamel from artificial lesions with clinically insignificant over-preparation of sound tissue, indicating technique selectivity towards grossly demineralised enamel. Alumina air abrasion resulted in substantial enamel removal in both sound and demineralised tissues indicating the operator selectivity required to use the techniques effectively in clinical practice.

An investigation of the role of auditory cortex in sound localization using muscimol-releasing Elvax.

Lesion studies suggest that primary auditory cortex (A1) is required for accurate sound localization by carnivores and primates. In order to elucidate further its role in spatial hearing, we examined the behavioural consequences of reversibly inactivating ferret A1 over long periods, using Elvax implants releasing the GABA(A) receptor agonist muscimol. Sub-dural polymer placements were shown to deliver relatively constant levels of muscimol to underlying cortex for >5 months. The measured diffusion of muscimol beneath and around the implant was limited to 1 mm. Cortical silencing was assessed electrophysiologically in both auditory and visual cortices. This exhibited rapid onset and was reversed within a few hours of implant removal. Inactivation of cortical neurons extended to all layers for implants lasting up to 6 weeks and throughout at least layers I-IV for longer placements, whereas thalamic activity in layer IV appeared to be unaffected. Blockade of cortical neurons in the deeper layers was restricted to < or = 500 microm from the edge of the implant, but was usually more widespread in the superficial layers. In contrast, drug-free Elvax implants had little discernible effect on the responses of the underlying cortical neurons. Bilateral implants of muscimol-Elvax over A1 produced significant deficits in the localization of brief sounds in horizontal space and particularly a reduced ability to discriminate between anterior and posterior sound sources. The performance of these ferrets gradually improved over the period in which the Elvax was in place and attained that of control animals following its removal. Although similar in nature, these deficits were less pronounced than those caused by cortical lesions and suggest a specific role for A1 in resolving the spatial ambiguities inherent in auditory localization cues.

Spatial and temporal properties of visual responses in the thalamus of the developing ferret.

Spatiotemporal patterning of neural activity is thought to influence the development of connections in the visual pathway. This patterning can arise spontaneously or through sensory experience. Here, we use a combination of natural and simple stimuli to investigate which elements of the visual environment modulate the earliest responses in the primary visual pathway of developing ferrets. Recordings were made during the first 2 weeks of visual responsiveness, which, in the ferret, overlaps with the period that the eyelids have not yet opened. Even when the eyelids are closed, both thalamic and cortical activity was found to be temporally modulated under conditions of natural visual stimulation. The modulations correlated with temporal changes in stimulus contrast but also reflected spatial structure in the visual scene. Simple stimuli were used to show that early responses to naturalistic stimuli are influenced by the localization and structure of through-the-eyelid receptive fields. The early visual responses were also characterized by substantial variability in the ability of the cells to detect stimuli of different duration and different intensity, in a temporally precise manner. These temporal and spatial properties should constrain how plasticity mechanisms interpret naturally patterned activity.