Integrins are transmembrane heterodimeric (αβ) receptors that transduce mechanical signals between the extracellular milieu and the cell in a bidirectional manner. Extensive research has shown that the integrin beta (β) family is widely expressed in the brain and that they control various aspects of brain development and function. Schizophrenia is a relatively common neurological disorder of unknown etiology and has been found to be closely related to neurodevelopment and neurochemicals in neuropathological studies of schizophrenia. Here, we review literature from recent years that shows that schizophrenia involves multiple signaling pathways related to neuronal migration, axon guidance, cell adhesion, and actin cytoskeleton dynamics, and that dysregulation of these processes affects the normal function of neurons and synapses. In fact, alterations in integrin β structure, expression and signaling for neural circuits, cortex, and synapses are likely to be associated with schizophrenia. We explored several aspects of the possible association between integrin β and schizophrenia in an attempt to demonstrate the role of integrin β in schizophrenia, which may help to provide new insights into the study of the pathogenesis and treatment of schizophrenia.

Intracellular recordings from thalamocortical (TC) neurons in the ventrolateral (VL) nucleus as well as paired intracellular recordings from TC-VL neurons and area 4 cortical neurons under ketamine-xylazine anesthesia were performed to study changes in hyperpolarization-rebound sequences evoked by successive stimuli to the dorsal thalamus at different frequencies and the impact of these changes at the cortical level. The cellular mechanisms of such changes in synaptic networks connecting TC with cortical neurons are relevant for short-term plasticity during low-frequency oscillatory activities. The progressive decrease in hyperpolarization of TC cells in response to single thalamic stimulus above a certain frequency (generally >1 Hz) and to pulse-trains at 10 Hz was mainly due to synaptic factors and not to mechanisms intrinsic to TC cells, as revealed by comparing responses evoked by synaptic volleys to those elicited by hyperpolarizing current pulses mimicking the synaptically evoked hyperpolarization-rebound sequence. The decreased hyperpolarization to repetitive synaptic volleys, leading to a decreased number of action potentials in the post-inhibitory spike-burst, had an impact on cortical activities, being matched by a decreased rebound depolarization of cortical cell during repetitive augmenting responses. The alterations in hyperpolarization-rebound sequences upon repetitive stimulation, probably resulting from the decreased efficacy of connections between thalamic reticular (RE) neurons to TC connections, results in the dampening of activities sustaining normal, and possibly paroxysmal, oscillations in the TC network. Our results suggest that this phenomenon should be taken into account when analyzing complex activities, such as physiological and pathological oscillations.

The interplay between the intrinsic properties of thalamocortical (TC) neurons and synaptic potentials was investigated in vivo, in decorticated and intact-cortex cats, as well as in computational models to elucidate the possible mechanisms underlying the disruption of the spindle oscillation, a network phenomenon. We found that the low-threshold spikes (LTSs) in TC neurons were graded in their amplitude and latency to peak when elicited by current pulses or synaptic potentials from physiological levels of hyperpolarization. IPSPs could either delay or shunt the LTSs. Although the onset of spindles was rhythmic and did not include rebound LTSs, the end of spindles was highly aperiodic suggesting that desynchronization could contribute to the spindle termination. The desynchronization could have several sources, the main of which are (a) intrinsically generated rebound LTSs in TC neurons that occur with different delays and keep thalamic reticular (RE) neurons relatively depolarized, and/or (b) out-of-phase firing of cortical neurons due to intracortical processes that would result in depolarization of both TC and RE neurons. The present study suggests that an active cortical network participates in disrupting the spindle activities. We propose that the progression of spindles contains at least three different phases, with different origins: (a) the onset is generated by RE neurons that impose their activity onto TC neurons, without participation of cortical neurons; (b) the middle part is produced by the interplay between RE and TC neurons, with potentiation from the cortical network; and (c) the waning of spindles is due to the out-of-phase firing of TC and particularly cortical neurons that participate in the spindle termination.