Developmental plasticity of inhibitory circuitry.
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Animals↗
Biomedical subjects
Sarah L Pallas
Publications and source records attributed to Sarah L Pallas.
A digital atlas to characterize the mouse brain transcriptome.
Massive amounts of data are being generated in an effort to represent for the brain the expression of all genes at cellular resolution. Critical to exploiting this effort is the ability to place these data into a common frame of reference. Here we have developed a computational method for annotating gene expression patterns in the context of a digital atlas to facilitate custom user queries and comparisons of this type of data. This procedure has been applied to 200 genes in the postnatal mouse brain. As an illustration of utility, we identify candidate genes that may be related to Parkinson disease by using the expression of a dopamine transporter in the substantia nigra as a search query pattern. In addition, we discover that transcription factor Rorb is down-regulated in the barrelless mutant relative to control mice by quantitative comparison of expression patterns in layer IV somatosensory cortex. The semi-automated annotation method developed here is applicable to a broad spectrum of complex tissues and data modalities.
Anatomy, Artistic↗
Neural mechanisms of stimulus velocity tuning in the superior colliculus.
Superior colliculus (SC)-mediated control of visuomotor behavior depends on neuronal selectivity for stimulus velocity. However, the mechanism responsible for velocity tuning in SC neurons is unclear. It was shown in a previous study of anesthetized, decorticate hamsters that the number and distribution of feed-forward retinal inputs are not critical for velocity tuning. Here the alternate hypothesis that inhibition from the surround determines velocity tuning of SC neurons was tested. Surround inhibition was present in 65% (43/66) of SC neurons recorded in the superficial gray layer. Neurons within this group that were selective for slowly moving stimuli exhibited spatially asymmetric surround inhibition, and their velocity tuning arose by preferential suppression of responses to rapidly moving stimuli. In the other 35% (23/66) of SC neurons recorded, surround inhibition was weak or absent and did not play a role in velocity tuning. Most neurons with surround inhibition were nonselective for the duration of stationary flashed stimuli, whereas neurons without surround inhibition were selective for stimulus duration. The majority of neurons that preferred intermediate or rapidly moving stimuli exhibited spatially symmetric surround inhibition. In these neurons, occluding the surround reduced velocity selectivity by enhancing responses to slowly moving stimuli. Based on these data, a model is proposed suggesting spatiotemporal interactions between inhibition and excitation that could underlie velocity tuning.
Action Potentials↗
The effect of oral 5-HTP administration on 5-HTP and 5-HT immunoreactivity in monoaminergic brain regions of rats.
5-Hydroxytryptophan (5-HTP), which is the rate-limiting precursor in serotonin (5-hydroxytryptamine (5-HT)) biosynthesis, is used as an oral supplement to enhance serotonin levels in humans. To evaluate its effects on serotonin levels and localization, 5-hydroxytryptophan was administered to Sprague-Dawley rats either orally or via intraperitoneal injection. 5-Hydroxytryptophan-immunoreactivity was co-localized with serotonin-immunoreactivity in the serotonergic dorsal raphe nucleus of control animals and this was not changed in animals given 5-hydroxytryptophan. Oral 5-HTP administration increased the intensity of both 5-HTP and serotonin immunoreactivity in raphe neurons. However, 5-HTP treatment also caused ectopic 5-hydroxytryptophan-immunoreactivity and serotonin-immunoreactivity in normally dopaminergic neurons of the substantia nigra par compacta. Serotonin-immunoreactivity was confined to neurons that also displayed amino acid decarboxylase immunoreactivity, but in a small percentage of substantia nigra neurons, serotonin immunoreactivity was not co-localized with tyrosine hydroxylase-immunoreactivity. The intensity of the immunoreactivity to serotonin and 5-hydroxytryptophan in the substantia nigra was maximal within 2h of 5-hydroxytryptophan administration and returned to control levels by 24h. This time course mirrored changes in HPLC measurements of 5-hydroxytryptophan, serotonin, and the metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the urine. 5-Hydroxytryptophan administration did not cause ectopic appearance of either serotonin or 5-hydroxytryptophan in the noradrenergic locus coeruleus. These results suggest that a single oral dose of 5-HTP increases the 5-HTP and serotonin content of serotonergic neurons and causes the transient ectopic appearance of serotonin in some normally non-serotonergic neurons.
5-Hydroxytryptophan↗
NMDA receptor blockade in the superior colliculus increases receptive field size without altering velocity and size tuning.
Neonatal brain injury triggers compensatory processes that can be adaptive or detrimental, but little is known about the mechanisms of compensation or how they might affect the response properties of neurons within the injured region. We have studied this issue in a rodent model. Partial ablation of the hamster superior colliculus (SC) at birth results in a compressed but complete visual field map in the remaining SC and a compensatory conservation of receptive field (RF) size and stimulus velocity and size tuning. The circuit underlying stimulus tuning in this system or its preservation after brain lesions is not known. Our previous work has shown that N-methyl-d-aspartate (NMDA) receptors are necessary for the development and conservation of RF size after partial SC ablation. In this study, we examined whether NMDA receptor function is also necessary for the development and conservation of stimulus velocity and size tuning. We found that velocity and size tuning were unaffected by chronic postnatal blockade of NMDA receptors and the resulting increases in RF size. Thus NMDA receptors in the SC are not necessary for the development of stimulus velocity and size tuning or in the compensatory maintenance of these properties following brain damage. These results suggest that stimulus velocity and size tuning may arise in the retina or from NMDA receptor-independent circuitry intrinsic to SC. The lack of conflict between NMDA receptor activity-dependent and -independent processes may allow conservation of some RF properties while others change during injury-induced or evolutionary changes in afferent/target convergence.
2-Amino-5-phosphonovalerate↗
Dark rearing reveals the mechanism underlying stimulus size tuning of superior colliculus neurons.
Neurons in the superficial layers of the midbrain superior colliculus (SC) exhibit distinct tuning properties for visual stimuli, but, unlike neurons in the geniculocortical visual pathway, most respond best to visual stimuli that are smaller than the classical receptive field (RF). The mechanism underlying this size selectivity may depend on the number and pattern of feedforward retinal inputs and/or the balance between inhibition and excitation within the RF. We have previously shown that chronic blockade of NMDA receptors (NMDA-R), which increases the convergence of retinal afferents onto SC neurons, does not alter size selectivity in the SC. This suggests that the number of retinal inputs does not determine size selectivity. Here we show, using single unit extracellular recordings from the SC of normal hamsters, that size selectivity in neurons selective for small stimulus size is correlated with the strength of inhibition within the RF. We also show that dark rearing causes concomitant reductions in both inhibition and size selectivity. In addition, dark rearing increases the percentage of neurons non-selective for stimulus size. Finally, we show that chronic blockade of NMDA-R, a procedure that does not alter size tuning, also does not change the strength of inhibition within the RF. Taken together, these results argue that inhibition within the RF underlies selectivity for small stimulus size and that inhibition must be intact for size tuning to be preserved after developmental manipulations of activity. In addition, these results suggest that regulation of the balance between excitation and inhibition within the RF does not require NMDA-R activity but does depend on visual experience. These results suggest that developmental experience influences neural response properties through an alteration of inhibitory circuitry.
2-Amino-5-phosphonovalerate↗