The influence of the environment on animal behavior has long been documented. Several anatomical and physiological studies have clearly demonstrated an involvement of the hippocampus and related structures (Green and Greenough, 1986
; Foster et al., 2000
; Sharp et al., 1985
; Faherty et al., 2003
; Foster and Dumas, 2001
). Recently more attention has been focused on how EE affects other brain areas, including the neocortex (Nithianantharajah et al., 2004
). In particular, large anatomical rearrangements of dendritic processing has been documented in the parietal cortex (Leggio et al., 2005
), prefrontal cortex (Dierssen et al., 2003
) as well as in monoaminergic neocortical innervation (Zhu et al., 2005
; Hellemans et al., 2005
). In the cat primary visual cortex, EE has been found to be effective in rescuing ocular dominance columns impaired by dark rearing (Bartoletti et al., 2004
). In the primary auditory cortex, EE induces major physiological rearrangements, detected as changes in single cell response properties as well as in scalp recording (Engineer et al., 2004
; Percaccio et al., 2005
Our results showed a strong and selective increase in amplitude and a change in kinetics of glutamatergic responses. These data are in agreement with the general increase in the excitability, firing rate and decrease in latency in the AEP amplitude observed in the response to short (25 ms) tones in vivo
(Engineer et al., 2004
The stability of the ratio between NMDAR-mediated and AMPAR-mediated currents indicates that EE is not associated with a selective insertion of new AMPARs in the postsynaptic membrane (“silent” synapse “awakening”). Yet, other postsynaptic changes preserving IAMPA/INMDA might take place at EE synapses.
The dramatic increase in EPSC amplitude might simply reflect an increase in the total number of excitatory spines, in agreement with previous findings (Dierssen et al., 2003
). Similarly, the lack of changes in eEPSC PPR at short (<500ms) IPIs does not allow to exclude the presence of presynaptic rearrangements preserving PPR. This interpretation is corroborated by the observation of a larger number of cells receiving high-frequency mEPSC, suggesting an increase in either the number of presynaptic fibers projecting to a subset of neurons, or in the capability of releasing neurotransmitter in a subset of presynaptic fibers.
The lack of changes in inhibitory responses do not support a major role for inhibition in the EE-driven re-shaping of auditory cortical responses. A sharp-electrode study on hippocampal non-pharmacologically dissected synaptic currents reported similar conclusion (Foster and Dumas, 2001
), although the invariance of inhibitory responses might be a reflection of the heterogeneity of cortical interneuronal types.
The increase in synaptic efficacy could be the result of a generalized synaptic strengthening or could be a layer-specific phenomenon. The unchanged excitatory responses from layer V would suggest the second hypothesis, indicating layer II/III as a privileged substrate for the solidification of cortical plasticity. A similar conclusion was previously reached with an anatomical-morphological study (Johansson and Belichenko, 2002
), and is expected if EE is caused by spike-time-dependent plasticity, since the threshold for action potentials in layer V is approximately 10 mV more positive than in layer II/III (Atzori et al., 2004
The increase in synaptic amplitude after exposure to the EE might derive from the transformation of low-probability and small amplitude synapses into high probability, large amplitude synapses (Atzori et al., 2001
). Yet, high probability synapses possess slower rise times and smaller PPR with respect to low-probability synapses, contrasting with our current finding that EE decreases rise-time and leaves PPR unchanged, suggesting a different origin for the synaptic changes in EE.
The use of a computational model corroborated the hypothesis that the increase in auditory gating in EE (Percaccio et al., 2005
) is due in part or completely to local, cortico-cortical changes in excitatory synaptic strength.
Auditory information is largely conveyed by low frequency envelope signals surfacing onto AI with slight phase differences within an isofrequency contour. Our computational model showed that the synaptic changes associated with the EE not only produce an expectable increase in firing rate but that they also decrease the dependence of the postsynaptic firing rate on the input phase differences, in the case of two slow frequency de-phased inputs. In fact, at all studied input frequencies, the increase in firing rate corresponding to a small phase increase displayed in control is replaced in EE by a solid enhancement almost independent on the phase difference between the two inputs, making synaptic summation more robust in EE.
Although our data indicate that EE causes significant cortical plasticity, we cannot exclude the possibility that non cortical auditory relays are also modified by EE, introducing a further component to the EE-induced alteration of the cortical signal detected by AEP (Percaccio et al., 2005
). In conclusion, we demonstrated for the first time that EE induces a change in the efficacy of glutamatergic synapses within the primary auditory cortex, associated with a major postsynaptic rearrangement compatible with an increase in the total number of synaptic connections.