ABSTRACT
Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assessing sensorimotor integration and whisker-based sensory discrimination as shown in the beam balance/walking test and sandpaper tactile discrimination test, respectively. At P25-31, spontaneous network activity in the barrel cortex in vivo was higher in KO mice compared with WT littermates, but not at P16-19. At P16-19, sensory evoked cortical responses in vivo elicited by single whisker stimulation were comparable in KO and WT mice. In contrast, at P25-31 evoked responses were smaller in amplitude and longer in duration in WT animals, whereas KO mice revealed no such developmental changes. In thalamocortical slices from KO mice, spontaneous activity was increased already at P16-19, and glutamatergic thalamocortical inputs to Layer 4 spiny stellate neurons were potentiated. We conclude that genetic ablation of PRG-1 modulates already at P16-19 spontaneous and evoked excitability of the barrel cortex, including enhancement of thalamocortical glutamatergic inputs to Layer 4, which distorts sensory processing in adulthood.
Subject(s)
Calmodulin-Binding Proteins/metabolism , Nerve Tissue Proteins/metabolism , Neurons/metabolism , Somatosensory Cortex/metabolism , Synaptic Transmission/physiology , Thalamus/metabolism , Vibrissae/physiology , Animals , Calmodulin-Binding Proteins/genetics , Female , Glutamic Acid/metabolism , Male , Mice, Knockout , Nerve Tissue Proteins/genetics , Neural Pathways/growth & development , Neural Pathways/metabolism , Neuronal Plasticity/physiology , Patch-Clamp Techniques , Postural Balance/physiology , Somatosensory Cortex/growth & development , Thalamus/growth & development , Tissue Culture Techniques , Touch Perception/physiology , Walking/physiologyABSTRACT
The amygdala is a brain region involved in the regulation of anxiety-related behavior. The purpose of this study was to correlate anxiety-related behavior of inbred mouse strains (BA//c, BALB/cJ, C3H/HeJ, C57BL/6J, CPB-K, DBA/2J, NMRI) to receptor binding in the amygdala. Binding site densities of receptors (NMDA, AMPA, kainate, GABA(A), serotonin, muscarinergic M(1)-M(2)) were measured with quantitative receptor autoradiography using tritiated ligands. Measurements of fear-sensitized acoustic startle response (ASR; induced by footshocks), elevated plus maze (EPM) behavior and receptor binding studies showed differences between the strains except for AMPA and muscarinergic M(2) receptors. Factor analysis revealed a Startle Factor with positive loadings of the density of serotonin and kainate receptors, and the amplitudes of the baseline and fear-sensitized ASRs. A second Anxiety-related Factor only correlated with the fear-sensitized ASR and anxiety parameters on the EPM but not receptor densities. There were also two General Activity Factors defined by (negative) correlations with entries to closed arms of the EPM. Because the density of NMDA and muscarinergic M(1) receptors also correlated negatively with the two factors, these receptors had a positive effect on general activity. In contrast, correlations of GABA(A), serotonin, and kainate receptors had the opposite sign as compared to closed arm entries. It is concluded that hereditary variations in the amygdala, particularly in kainate and serotonin receptors, play a role for the baseline and fear-sensitized ASR, whereas the general activity is influenced by many neurotransmitter receptor systems.