Neuroscience
-
Many neurons tend to fire clusters of action potentials called bursts followed by quiescence in response to sensory input. While the mechanisms that underlie burst firing are generally well understood in vitro, the functional role of these bursts in generating behavioral responses to sensory input in vivo are less clear. Pyramidal cells within the electrosensory lateral line lobe (ELL) of weakly electric fish offer an attractive model system for studying the coding properties of burst firing, because the anatomy and physiology of the electrosensory circuitry are well understood, and the burst mechanism of ELL pyramidal cells has been thoroughly characterized in vitro. ⋯ These correlations were much weaker in magnitude than those observed in vitro. More surprisingly, our results show that correlations between burst and stimulus attributes actually decreased in magnitude when we used low frequency stimuli that are expected to promote burst firing. We propose that this discrepancy is attributable to differences between ELL pyramidal cell burst firing under in vivo and in vitro conditions.
-
Much of the cognitive decline shown by aging primates can be attributed to dysfunction of prefrontal cortex and, as shown previously, about 30% of asymmetric (excitatory) and symmetric (inhibitory) axodendritic synapses are lost from the neuropil of layer 2/3 in prefrontal area 46 with age [Peters A, Sethares C, Luebke JI (2008) Neuroscience 152:970-981]. Whether there is a similar loss of inhibitory axosomatic synapses from this cortex has not been determined, but a study in primate motor cortex suggests that axosomatic synapses are not lost with age [Tigges J, Herndon JG, Peters A (1992) Anat Rec 232:305-315]. The present study is focused upon whether the remaining axon terminals forming inhibitory synapses in old monkeys hypertrophy to compensate for any age-related loss. ⋯ We also show that among these age-related changes, only the numbers of synaptic vesicles in axosomatic synapses are significantly correlated with the cognitive impairment indices displayed by the same monkeys. In summary, the data provide original evidence that axosomatic axon terminals increase in size and in their content of mitochondria and synaptic vesicles. Furthermore, based on our and previously published results, we speculate that these changes are linked to age-related cognitive decline.
-
Dendritic spines contain a family of abundant scaffolding proteins known as Shanks, but little is known about how their distributions might change during synaptic activity. Here, pre-embedding immunogold electron microscopy is used to localize Shanks in synapses from cultured hippocampal neurons. We find that Shanks are preferentially located at postsynaptic densities (PSDs) as well as in a filamentous network near the PSD, extending up to 120 nm from the postsynaptic membrane. ⋯ Depolarization with high K+ for 2 min causes transient, reversible translocation of Shanks towards the PSD that is dependent on extracellular Ca2+. The amount of activity-induced redistribution and subsequent recovery is pronounced for Shank1 but less so for Shank2. Thus, Shank1 appears to be a dynamic element within the spine, whose translocation could be involved in activity-induced, transient structural changes, while Shank2 appears to be a more stable element positioned at the interface of the PSD with the spine cytoplasm.
-
We analyzed the effects of different treadmill running protocols on the functional recovery after chronic constriction injury (CCI) of the sciatic nerve in mice. We found that a treadmill protocol of short-lasting running (1 h/d for 5 days after CCI) reduced the neuropathy-induced mechanical allodynia and normalized the weight bearing and the sciatic static index of the injured hindpaw. At difference, a treadmill protocol of long-lasting running (1 h/d for more than 5 days after CCI) was unfavorable both for allodynia and for functional recovery. ⋯ Finally, in sections of injured sciatic nerves, we analyzed the expression of Cdc2 and GAP-43 proteins that are both up-regulated during peripheral regenerative processes. Compared to mice subjected to long-lasting treadmill running, mice subjected to short-lasting treadmill running showed an acceleration of the regenerative processes at the injured sciatic nerve. Our data demonstrate that short-lasting treadmill running, by reducing the neuropathic pain symptoms and facilitating the regenerative processes of the injured nerve, have beneficial rehabilitative effects on the functional recovery after peripheral nerve injury.
-
Many dopaminergic neurons exhibit a short-latency response to noxious stimuli, the source of which is unknown. Here we report that the nociceptive-recipient parabrachial nucleus appears to be a critical link in the transmission of pain related information to dopaminergic neurons. Injections of retrograde tracer into the substantia nigra pars compacta of the rat labelled neurons in both the lateral and medial parts of the parabrachial nucleus, and intra-parabrachial injections of anterograde tracers revealed robust projections to the pars compacta and ventral tegmental area. ⋯ Intra-parabrachial injections of the local anaesthetic lidocaine or the GABA(A) receptor antagonist muscimol reduced tonic parabrachial activity and the amplitude (and in the case of lidocaine, duration) of the phasic response to footshock. Suppression of parabrachial activity with lidocaine reduced the baseline firing rate of dopaminergic neurons, while both lidocaine and muscimol reduced the amplitude of the phasic inhibitory response to footshock, in the case of lidocaine sometimes abolishing it altogether. Considered together, these results suggest that the parabrachial nucleus is an important source of short-latency nociceptive input to the dopaminergic neurons.