Reducing Contralateral SI Activity Reveals Hindlimb Receptive Fields in the SI Forelimb-Stump Representation of Neonatally Amputated Rats

Abstract

Pluto, Charles P., Nicolas L. Chiaia, Robert W. Rhoades, and Richard D. Lane. Reducing contralateral SI activity reveals hindlimb receptive fields in the SI forelimb-stump representation of neonatally amputated rats. J Neurophysiol 94: 1727-1732, 2005. First Published March 30, 2005 doi:10.1152/jn.00228.2005. In adult rats that sustained forelimb amputation on the day of birth, Ͼ30% of multiunit recording sites in the forelimb-stump representation of primary somatosensory cortex (SI) also respond to cutaneous hindlimb stimulation when cortical GABA AϩB receptors are blocked (GRB). This study examined whether hindlimb receptive fields could also be revealed in forelimb-stump sites by reducing one known source of excitatory input to SI GABAergic neurons, the contralateral SI cortex. Corpus callosum projection neurons connect homotopic SI regions, making excitatory contacts onto pyramidal cells and interneurons. Thus in addition to providing monosynaptic excitation in SI, callosal fibers can produce disynaptic inhibition through excitatory synapses with inhibitory interneurons. Based on the latter of these connections, we hypothesized that inactivating the contralateral (intact) SI forelimb region would "unmask" normally suppressed hindlimb responses by reducing the activity of SI GABAergic neurons. The SI forelimbstump representation was first mapped under normal conditions and then during GRB to identify stump/hindlimb responsive sites. After GRB had dissipated, the contralateral (intact) SI forelimb region was mapped and reversibly inactivated with injections of 4% lidocaine, and selected forelimb-stump sites were retested. Contralateral SI inactivation revealed hindlimb responses in ϳ60% of sites that were stump/hindlimb responsive during GRB. These findings indicate that activity in the contralateral SI contributes to the suppression of reorganized hindlimb receptive fields in neonatally amputated rats. I N T R O D U C T I O NNeuron clusters in the SI forelimb-stump representation of adult rats that sustained neonatal forelimb amputation normally have receptive fields located exclusively on the stump. However, when cortical GABA AϩB receptors are blocked (GRB), many of these recording sites exhibit an additional receptive field located on the ipsilateral hindlimb (Lane et al. 1997).Results from previous studies suggest that these hindlimb inputs originate in the SI hindlimb representation in the same hemisphere and are transmitted to SI forelimb-stump neurons via a polysynaptic circuit through the intervening dysgranular cortex (Lane et al. 1999;Stojic et al. 2001). Hindlimb responses can be revealed when GRB is induced globally by topical application or locally by injection at the recording site, suggesting that the GABA receptors of interest are located on hindlimb responsive forelimb-stump neurons and/or on axons of other cells carrying hindlimb information into the deafferented region (Pluto et al. 2004). Because inhibitory interneurons typically have relatively short axons that synapse locally, it is lik...

Ipsilateral Whiskers Suppress Experience-Dependent Plasticity in the Barrel Cortex

“…Ipsilateral sensory inputs may normally reduce contralaterally driven activity in the cortex and sharpen response properties by reducing surround receptive fields of cortical neurons (Shuler et al, 2001;Pluto et al, 2005;Schmidt et al, 2006). Our data indicate that the cumulative effect of reduced ipsilateral sensory activity is an increase in stimulus-driven activity in the sensoryspared hemisphere.…”

“…Although transection of the corpus callosum, the main anatomical structure that connects the two cortical hemispheres, results in only subtle sensory and motor deficits (Gazzaniga, 2000), many studies have confirmed that cortical neuron responses can be strongly influenced by activation of peripheral ipsilateral inputs (Armstrong-James and George, 1988;Clarey et al, 1996;Shuler et al, 2001Shuler et al, , 2002Pluto et al, 2005).…”

“…The clear anatomy of the rodent somatosensory cortex, where individual whiskers project to topographically defined cortical columns (Woolsey and Van der Loos, 1970), as well as the complete crossing of primary sensory afferents at the midline (Waite, 1969;Smith, 1973;Erzurumlu and Killackey, 1980), makes this an attractive system to study the influence of interhemispheric interactions in shaping receptive field properties (Clarey et al, 1996;Shuler et al, 2001Shuler et al, , 2002Pluto et al, 2005). In the rodent, it has been observed that deflection of ipsilateral whiskers suppresses cortical responses evoked by contralateral whisker stimulation (Shuler et al, 2001), consistent with other anatomical (Carr and Sesack, 1998) and electrophysiological (Kawaguchi, 1992) evidence supporting the conclusion that, under normal conditions, callosal inputs have a net inhibitory influence.…”

Cross-Sensory Modulation of Primary Sensory Cortex Is Developmentally Regulated by Early Sensory Experience

“…DGZ also projects directly to S1 barrel cortex (Chapin et al, 1987;Koralek et al, 1990). Moreover, since horizontal connections in cortex including somatosensory cortex have been shown to recruit inhibitory networks under some conditions (Tucker and Katz, 2003;Pluto et al, 2005;Keniston et al, 2010), it is possible that the projections from the DGZ to barrel cortex terminate on inhibitory FSUs that could cause subthreshold changes leading to an increased excitability in inhibitory neurons. Thus, this model predicts that the click component of the CS stimulus would activate the DGZ, which could increase the excitability of the FSUs in barrel cortex via corticocortical connections leading to a suppression of firing in the longer latency component of the barrel field responses.…”

Ipsilateral Input Modifies the Primary Somatosensory Cortex Response to Contralateral Skin Flutter

“…Schnitzler et al (1995), using magnetoencephalography (MEG), reported that concurrent tactile stimulation of the ipsilateral hand enhances the response of SI to stimulation of the contralateral median nerve. Conversely, (1) Korvenoja et al (1995) reported that the SI activation (detected using MEG) evoked by contralateral median nerve stimulation is suppressed during ipsilateral hand movement, (2) functional magnetic resonance imaging studies in both monkeys (Lipton et al, 2006) and humans (Hlushchuk et al, 2006) showed that an ipsilateral skin stimulus evokes CNS actions that partially suppress the SI response to a contralateral stimulus, (3) destruction of SI in one hemisphere (rats) was shown to be accompanied by the appearance (in the opposite SI) of neurons with bilateral receptive fields [interpreted to indicate that SI activity exerts a suppressive influence on SI neurons in the opposite hemisphere (Pluto et al, 2005)], and (4) low-frequency transcranial magnetic stimulation of sensorimotor cortex (in humans, Pal et al, 2005) was found to reduce excitability in the opposite hemisphere. Viewed collectively, these findings raise the possibility that the response of the SI hand region to a tactile stimulus (and thus the stimulus-evoked perceptual experience) may be subject to modulatory influences arising from the ipsilateral hand.…”