Adenosine Alters Plasticity Rules in Developing Cortex
Irene Martínez-Gallego, Mikel Pérez-Rodríguez, Heriberto Coatl-Cuaya, Gonzalo Flores, and Antonio Rodríguez-Moreno
(see pages 6038–6052)
During nervous system development, an initial period of prolific synaptogenesis is followed by a period of enhanced plasticity, in which synapses are strengthened or eliminated by activity-dependent processes. Although such refinement continues throughout life, some forms of plasticity are lost or weakened, and rules for inducing plasticity can change as circuits mature. In the somatosensory cortex of young mice, for example, synapses between layer 4 (L4) and L2/3 pyramidal cells are weakened if the postsynaptic L2/3 cell spikes just before the presynaptic L4 cell (post-before-pre pairing), but this spike timing-dependent long-term depression (t-LTD) disappears after postnatal day 28 (P28). Martínez-Gallego et al. investigated the mechanisms underlying this loss of t-LTD and discovered that post-before-pre pairing induces spike timing-dependent long-term potentiation (t-LTP) after P60.
The authors first asked whether adenosine A1 receptors (A1Rs), which modulate plasticity in other brain areas, are involved in preventing t-LTD after P28 in somatosensory cortex. Indeed, applying an A1R antagonist allowed t-LTD to be evoked in cortical slices from mice aged P28–P37. Conversely, an A1R agonist prevented t-LTD induction before P28. In fact, at higher agonist concentrations, post-before-pre pairing evoked t-LTP in slices from mice aged P13–P27.
Activation of presynaptic A1Rs reduces glutamate release, and thus reduces the slope of EPSPs. Notably, blocking A1Rs increased the slope of evoked EPSPs in cortical slices from young mice, but the effect was greater at P28–P37 and greater still at P37–P60. This suggests that adenosine signaling continues to increase into adulthood. Similar to the effects of increasing A1R agonist levels in young mice, the increase in endogenous adenosine levels after P37 caused post-before-pre pairing to evoke t-LTP. This t-LTP required activation of NMDA and metabotropic glutamate receptors, increases in postsynaptic calcium levels mediated by influx through L-type calcium channels and release from intracellular stores, production of nitric oxide by postsynaptic neurons, and release of gliotransmitters from astrocytes, in addition to activation of A1Rs.
Altogether, the results suggest that increases in extracellular adenosine levels, likely resulting from increased release of its precursor, ATP, from astrocytes, gradually changes the rules for plasticity induction during maturation of the somatosensory cortex. When adenosine levels are low, post-before-pre pairing evokes t-LTD. As levels rise, t-LTD is lost and is eventually replaced by t-LTP.
Post-before-pre pairing causes t-LTD (black) in somatosensory cortex of young mice, but causes t-LTP if A1Rs are sufficiently activated (red). See Martínez-Gallego et al. for details.
Central Medial Thalamic Nucleus Promotes Cautiousness
Mohammad M. Herzallah, Alon Amir, and Denis Paré
(see pages 6053–6068)
When foraging for food, prey animals often encounter predators, forcing them to balance their need to eat against their need not to be eaten. Many brain areas contribute to this calculation, including the amygdala. Inactivating the basolateral amygdala (BLA) increases the willingness of rats to venture away from a safe nest box when given the opportunity to retrieve food in the presence of a robotic predator. Because the central medial thalamic (CMT) nucleus projects strongly to the BLA, Herzallah et al. asked whether it also contributes to foraging behavior.
Inactivating CMT, like inactivating BLA, reduced the amount of time rats lingered near the entrance of the nest box and increased the distance rats traveled to obtain food in the presence of a predator. Electrophysiological recordings showed that the activity of most CMT neurons was significantly altered during at least one phase of the foraging task (waiting at the nest door, approaching food, and/or retreating to the nest). Responses were heterogeneous, however, with some neurons showing increases in firing and others showing decreases. Moreover, many neurons had different responses on the same task phase depending on whether the predator was present or absent; on average, firing rates were lower when the predator was present. Surprisingly, although CMT projections to the BLA are glutamatergic and mainly target principal cells, the modulation of CMT neurons during the foraging task was inversely correlated with modulation of BLA principal neurons and positively correlated with modulation of BLA fast-spiking interneurons. A generalized linear model failed to pinpoint specific factors (such as food retrieval or predator approach) driving activity modulation in CMT, however.
These results suggest that CMT neurons contribute to multiple aspects of foraging behavior. But how it exerts its influence remains unclear. Future work will have to reconcile the apparently contradictory findings that activity of CMT and BLA principal neurons is inversely correlated during foraging tasks, yet inactivation of either nucleus increases caution in the presence of predators.
Footnotes
This Week in The Journal was written by Teresa Esch, Ph.D.
