The Current Status of Somatostatin-Interneurons in Inhibitory Control of Brain Function and Plasticity

The mammalian neocortex contains many distinct inhibitory neuronal populations to balance excitatory neurotransmission. A correct excitation/inhibition equilibrium is crucial for normal brain development, functioning, and controlling lifelong cortical plasticity. Knowledge about how the inhibitory network contributes to brain plasticity however remains incomplete. Somatostatin-(SST-) interneurons constitute a large neocortical subpopulation of interneurons, next to parvalbumin-(PV-) and vasoactive intestinal peptide-(VIP-) interneurons. Unlike the extensively studied PV-interneurons, acknowledged as key components in guiding ocular dominance plasticity, the contribution of SST-interneurons is less understood. Nevertheless, SST-interneurons are ideally situated within cortical networks to integrate unimodal or cross-modal sensory information processing and therefore likely to be important mediators of experience-dependent plasticity. The lack of knowledge on SST-interneurons partially relates to the wide variety of distinct subpopulations present in the sensory neocortex. This review informs on those SST-subpopulations hitherto described based on anatomical, molecular, or electrophysiological characteristics and whose functional roles can be attributed based on specific cortical wiring patterns. A possible role for these subpopulations in experience-dependent plasticity will be discussed, emphasizing on learning-induced plasticity and on unimodal and cross-modal plasticity upon sensory loss. This knowledge will ultimately contribute to guide brain plasticity into well-defined directions to restore sensory function and promote lifelong learning

BDNF expression in cat striate cortex is regulated by binocular pattern deprivation

Deprivation of patterned visual information, as in early onset congenital cataract patients, results in a severe impairment in global motion perception. Previously we reported a delayed maturation of the peripheral visual field representation in primary visual area 17, based on a 2‑D DIGE screen for protein expression changes and in situ hybridization for the activity reporter gene ZIF268. To corroborate these findings we here explore the binocular pattern deprivation (BD)‑regulated expression of brain‑derived neurotrophic factor (BDNF), a well‑described neurotrophin precipitously regulated by early visual experience. To assess the timing of maturation‑related BDNF expression we compared the central and the peripheral visual field representations of area 17 of 1, 2, 4 and 6‑month‑old and adult cats reared under normal visual conditions. To scrutinize the outcome of BD, four different deprivation strategies were compared, including early onset BD from birth and lasting for 2, 4 or 6 months (2BD, 4BD, 6BD), and late onset BD for 2 months upon 2 months of normal vision (2N2BD), as animal models of congenital and delayed onset cataract. During normal cortical development the BDNF transcript levels, measured by quantitative RT‑PCR, remained stable. Higher BDNF mRNA levels were found in central area 17 of 2BD and 6BD animals compared to age‑matched controls. In central area 17, the high BDNF mRNA levels at the end of the BD period may activate a mechanism by which plastic processes, halted by deprivation, may begin. We here confirm that the peripheral visual field representation of area 17 matures slower than its central counterpart. Only in central area 17 normal visual input upon BD could upregulate BDNF mRNA which may lead to a fast activation of local plastic adaptations

Dynamics of spatial frequency tuning in mouse visual cortex

Neuronal spatial frequency tuning in primary visual cortex (V1) substantially changes over time. In both primates and cats, a shift of the neuron\u27s preferred spatial frequency has been observed from low frequencies early in the response to higher frequencies later in the response. In most cases, this shift is accompanied by a decreased tuning bandwidth. Recently, the mouse has gained attention as a suitable animal model to study the basic mechanisms of visual information processing, demonstrating similarities in basic neuronal response properties between rodents and highly visual mammals. Here we report the results of extracellular single-unit recordings in the anesthetized mouse where we analyzed the dynamics of spatial frequency tuning in V1 and the lateromedial area LM within the lateral extrastriate area V2L. We used a reverse-correlation technique to demonstrate that, as in monkeys and cats, the preferred spatial frequency of mouse V1 neurons shifted from low to higher frequencies later in the response. However, this was not correlated with a clear selectivity increase or enhanced suppression of responses to low spatial frequencies. These results suggest that the neuronal connections responsible for the temporal shift in spatial frequency tuning may considerably differ between mice and monkeys

A proteomic approach to understand MMP?3?driven developmental processes in the postnatal cerebellum: Chaperonin CCT6A and MAP kinase as contributing factors

Matrix metalloproteinase?3 (MMP?3) deficiency in mice was previously reported to result in a transiently retarded granule cell migration at postnatal day 8 (P8) and a sustained disturbed arborization of Purkinje cell dendrites from P8 on, concomitant with a delayed synapse formation between granule cells and Purkinje cells and resulting in mild deficits in motor performance in adult animals. However, the molecular mechanisms by which MMP?3 contributes to proper development of the cerebellar cortex during the first postnatal weeks remains unknown. In this study, we used a functional proteomics approach to investigate alterations in protein expression in postnatal cerebella of wild?type versus MMP?3 deficient mice, and to further elucidate MMP?3?dependent pathways and downstream targets in vivo. At P8, two?dimensional difference gel electrophoresis and mass spectrometry identified 20 unique proteins with a different expression between the two genotypes. Subsequent “Ingenuity Pathway Analysis” and Western blotting indicate that the chaperonin containing T?complex polypeptide 1, subunit 6A and the MAP kinase signaling pathway play a key role in the MMP?3?dependent regulation of neurite outgrowth and neuronal migration in the developing brain

Posterior parietal cortex contributions to cross-modal brain plasticity upon sensory loss

status: Published onlin

A Highly Reproducible and Straightforward Method to Perform In Vivo Ocular Enucleation in the Mouse after Eye Opening

Enucleation or the surgical removal of an eye can generally be considered as a model for nerve deafferentation. It provides a valuable tool to study the different aspects of visual, cross-modal and developmental plasticity along the mammalian visual system(1-4). Here, we demonstrate an elegant and straightforward technique for the removal of one or both eyes in the mouse, which is validated in mice of 20 days old up to adults. Briefly, a disinfected curved forceps is used to clamp the optic nerve behind the eye. Subsequently, circular movements are performed to constrict the optic nerve and remove the eyeball. The advantages of this technique are high reproducibility, minimal to no bleeding, rapid post-operative recovery and a very low learning threshold for the experimenter. Hence, a large amount of animals can be manipulated and processed with minimal amount of effort. The nature of the technique may induce slight damage to the retina during the procedure. This side effect makes this method less suitable as compared to Mahajan et al. (2011)(5) if the goal is to collect and analyze retinal tissue. Also, our method is limited to post-eye opening ages (mouse: P10 - 13 onwards) since the eyeball needs to be displaced from the socket without removing the eyelids. The in vivo enucleation technique described in this manuscript has recently been successfully applied with minor modifications in rats and appears useful to study the afferent visual pathway of rodents in general.status: publishe

It takes two: Bilateral bed nuclei of the stria terminalis mediate the expression of contextual fear, but not of moderate cued fear

A growing body of research supports a prominent role for the bed nucleus of the stria terminalis (BST) in the expression of adaptive and perhaps even pathological anxiety. The traditional premise that the BST is required for long-duration responses to threats, but not for fear responses to distinct, short-lived cues may, however, be oversimplified. A thorough evaluation of the involvement of the BST in cued and contextual fear is therefore warranted. In a series of preregistered experiments using male Wistar rats, we first addressed the involvement of the BST in cued fear. Following up on earlier work where we found that BST lesions disrupted auditory fear while the animals were in a rather high stress state, we here show that the BST is not required for the expression of more specific fear for the tone under less stressful conditions. In the second part, we corroborate that the same lesion method does attenuate contextual fear. Furthermore, despite prior indications for an asymmetric recruitment of the BST during the expression of anxiety, we found that bilateral lesioning of the BST is required for a significant attenuation of the expression of contextual fear. A functional BST in only one hemisphere resulted in increased variability in the behavioral outcome. We conclude that, in animals that acquired a fear memory with an intact brain, the bilateral BST mediates the expression of contextual fear, but not of unambiguous cued fear.status: publishe