The Cellular Basis of GABA _B -Mediated Interhemispheric Inhibition

Abstract

Interhemispheric inhibition is thought to mediate cortical rivalry between the two hemispheres through callosal input. The long-lasting form of this inhibition is believed to operate via γ-aminobutyric acid type B (GABA(B)) receptors, but the process is poorly understood at the cellular level. We found that the firing of layer 5 pyramidal neurons in rat somatosensory cortex due to contralateral sensory stimulation was inhibited for hundreds of milliseconds when paired with ipsilateral stimulation. The inhibition acted directly on apical dendrites via layer 1 interneurons but was silent in the absence of pyramidal cell firing, relying on metabotropic inhibition of active dendritic currents recruited during neuronal activity. The results not only reveal the microcircuitry underlying interhemispheric inhibition but also demonstrate the importance of active dendritic properties for cortical output.

Tracking post-error adaptation in the motor system by transcranial magnetic stimulation

“…Previous studies have shown that the commission of an error engaged several regions involved in performance monitoring which resulted in either decreased activation or increased inhibition of the contralateral motor cortex (Marco-Pallare´s et al, 2008;Danielmeier and Ullsperger, 2011), which presumably might lead to the increase of excitability of the ipsilateral motor cortex shown in our data. Indeed, the reciprocal activation/ inhibition of the two hemispheres is thought to be mediated via transcallosal connections featuring inhibitory GABA B receptors (Irlbacher et al, 2007;Palmer et al, 2012). Importantly, MEPs in Experiments 1 and 2 were elicited after stimulation of the right hemisphere and acquired from the left FDI muscle, whereas all motor responses involved the left hemisphere/right hand.…”

Cortical neural populations can guide behavior by integrating inputs linearly, independent of synchrony

“…In this way, coincident synaptic inputs can be amplified relative to asynchronous inputs. In addition to this nonlinearity caused by spike threshold, other active processes such as dendritic calcium spikes (3)(4)(5) can preferentially amplify synchronous inputs. A variety of ways that timing could impact network function have been explored, including oscillatory synchronization (6,7), strong cascading effects of individual neurons or synapses (8)(9)(10)(11), and information encoding via temporal patterns (12).…”

Numerical modelling of plasticity induced by transcranial magnetic stimulation

“…This function incorporates the timecourse of the excitatory post-synaptic potential (EPSP). However, for the case of inhibitory synapses (b = i) we include the effects of both GABA A and the much longer lasting (several hundred milliseconds [32,34]) GABA B neurostransmitters. Therefore we use a combination of two of these functions for the inhibitory postsynaptic potential (IPSP):…”

“…Table 1 gives a list of standard parameters chosen for this modelling. Values for the mean-field cortical modelling have been chosen drawing from references [38,39,37,11,45,46], with smaller rates being used for α B and β B to model the long timescale GABA B inhibitory post-synaptic potentials [32,34]. Values for the STDP have been chosen with reference to [1] and [11].…”