This interference could be prevented by simultaneously enhancing the strength of excitatory transmission from pyramidal

cells to inhibitory interneurons. The enhanced activation of inhibitory currents prevented the excessive spread of activity within the network during learning and recall. This effect may prevent the breakdown of function due to the development of excessive associations between different stored activity patterns. This biophysical model has remarkable similarities to thought disorder in schizophrenic patients. Deficits in learning new verbal associations in the Verbal Paired Associate Learning Inhibitors,research,lifescience,medical Test, which also correlate with a reduced volume of the left posterior superior gyrus, have been demonstrated in schizophrenic patients.15 Impairment of recall may be reflected by the greater “search activity” for congruent sentence endings seen in the N400 studies conducted by McCarley et al.16 The capability of local interneurons to synchronize Inhibitors,research,lifescience,medical cortical network activity has already been mentioned. This triggers selleck screening library population bursts that may shape local functional connectivity in the cortex17, and also strengthen the overall excitatory limbic input onto mesolimbic Inhibitors,research,lifescience,medical GABAcrgic neurons. These neurons integrate cortical glutamatergic and the dopaminergic input from the ventral tegmentum. High synchronicity

of the cortical glutamatergic input is more likely to overcome the dopaminergic inhibition, leading downstream from the mesolimbic projection neuron finally Inhibitors,research,lifescience,medical to an improvement in the thalamic filter function.18 Some neuroleptics may exert a dual action in balancing the relationship between dopaminergic and glutamatergic input, eg, haloperidol, which also has glutamatergic agonist properties byenhancing NMDA receptor sensitivity.19-21 Another physiological correlate of the glutamatergic interplay between excitatory projection neurons and GABAergic interneurons

is γ-range neural synchronization.22 Inhibitors,research,lifescience,medical In an auditory evoked potential paradigm, schizophrenic patients are distinguished from controls by a reduced EEG power at 40 Hz, but not at lower frequencies of stimulation. They exhibit a delayed onset of entrainment, poorer synchronization, and any longer persistence of entrainment after the end of the 40-Hz stimulation, consistent with impaired generation of γ-synchronization.16 Adenosine The impact of age and gender on recurrent inhibition To further examine the compatibility of our model with schizophrenia, we conducted similar in vitro experiments on the impact of age and gender on recurrent inhibition. Aged rats of both sexes showed decreased amplitudes of the IPSPs (1.1 ±0.9 mV in rats of 9 to 12 months, compared with 6.7 ±0.5 mV in prepubescent rats). Only one third of all slices tested exhibited any measurable IPSP at all. The EPSP, however, appeared more prominent compared with juvenile rats.