No abstract

The timing of action potentials relative to sensory stimuli can be precise down to milliseconds in the visual system, even though the relevant timescales of natural vision are much slower. The existence of such precision contributes to a fundamental debate over the basis of the neural code and, specifically, what timescales are important for neural computation. Using recordings in the lateral geniculate nucleus, here we demonstrate that the relevant timescale of neuronal spike trains depends on the frequency content of the visual stimulus, and that 'relative', not absolute, precision is maintained both during spatially uniform white-noise visual stimuli and naturalistic movies. Using information-theoretic techniques, we demonstrate a clear role of relative precision, and show that the experimentally observed temporal structure in the neuronal response is necessary to represent accurately the more slowly changing visual world. By establishing a functional role of precision, we link visual neuron function on slow timescales to temporal structure in the response at faster timescales, and uncover a straightforward purpose of fine-timescale features of neuronal spike trains.

Until recently, neurons in the healthy brain were considered immune-privileged because they did not appear to express MHC class I (MHCI). However, MHCI mRNA was found to be regulated by neural activity in the developing visual system and has been detected in other regions of the uninjured brain. Here we show that MHCI regulates aspects of synaptic function in response to activity. MHCI protein is colocalized postsynaptically with PSD-95 in dendrites of hippocampal neurons. In vitro, whole-cell recordings of hippocampal neurons from ␤2m/TAP1 knockout (KO) mice, which have reduced MHCI surface levels, indicate a 40% increase in mini-EPSC (mEPSC) frequency. mEPSC frequency is also increased 100% in layer 4 cortical neurons. Similarly, in KO hippocampal cultures, there is a modest increase in the size of presynaptic boutons relative to WT, whereas postsynaptic parameters (PSD-95 puncta size and mEPSC amplitude) are normal. In EM of intact hippocampus, KO synapses show a corresponding increase in vesicles number. Finally, KO neurons in vitro fail to respond normally to TTX treatment by scaling up synaptic parameters. Together, these results suggest that postsynaptically localized MHCl acts in homeostatic regulation of synaptic function and morphology during development and in response to activity blockade. The results also imply that MHCI acts retrogradely across the synapse to translate activity into lasting change in structure.homeostatic ͉ neuron ͉ plasticity ͉ synapsin ͉ PSD-95 E xperience transduced into neural activity is required for proper brain development (1). The process by which neural activity remodels synaptic connections during development is termed ''activity-dependent plasticity,'' in which electrical signals induce specific patterns of gene transcription to alter synaptic properties and structural connectivity. Genes including BDNF and CamKII are known to be critical for this plasticity (2-4); however, many other molecules are likely involved as well.MHC class I (MHCI) family members are well known for their roles in cellular immunity, but a neuronal function has not been generally appreciated. In the immune system, MHCI genes act in concert with T cell receptors to discriminate self-versus non-self-proteins. The CNS was considered ''immune privileged,'' in part, because it was thought that healthy neurons do not express MHCI protein (5, 6). Recently, MHCI gene family members have been found at low levels in CNS neurons (7-11). MHCI mRNA is expressed and regulated in cortical and thalamic neurons during development and is down-regulated by chronic activity blockade with Tetrodotoxin (TTX) in vivo (7). MHCI is also a downstream target of the transcription factor CREB, required for Hebbian synaptic plasticity (8,12,13). MHCI is thus implicated in several forms of activity-dependent synaptic plasticity.The MHCI gene family includes Ͼ70 members in rodents (14). The proteins encoded are heavy chains comprising the largest portion of the MHCI protein complex. Functional MHCI is usually a trimer consisting...