In JoVE (1)

Other Publications (8)

Articles by Mark H. Shalinsky in JoVE

Other articles by Mark H. Shalinsky on PubMed

Muscarinic Activation of a Cation Current and Associated Current Noise in Entorhinal-cortex Layer-II Neurons

Journal of Neurophysiology. Sep, 2002  |  Pubmed ID: 12205141

The effects of muscarinic stimulation on the membrane potential and current of in situ rat entorhinal-cortex layer-II principal neurons were analyzed using the whole cell, patch-clamp technique. In current-clamp experiments, application of carbachol (CCh) induced a slowly developing, prolonged depolarization initially accompanied by a slight decrease or no significant change in input resistance. By contrast, in a later phase of the depolarization input resistance appeared consistently increased. To elucidate the ionic bases of these effects, voltage-clamp experiments were then carried out. In recordings performed in nearly physiological ionic conditions at the holding potential of -60 mV, CCh application promoted the slow development of an inward current deflection consistently associated with a prominent increase in current noise. Similarly to voltage responses to CCh, this inward-current induction was abolished by the muscarinic antagonist, atropine. Current-voltage relationships derived by applying ramp voltage protocols during the different phases of the CCh-induced inward-current deflection revealed the early induction of an inward current that manifested a linear current/voltage relationship in the subthreshold range and the longer-lasting block of an outward K(+) current. The latter current could be blocked by 1 mM extracellular Ba(2+), which allowed us to study the CCh-induced inward current (I(CCh)) in isolation. The extrapolated reversal potential of the isolated I(CCh) was approximately 0 mV and was not modified by complete substitution of intrapipette K(+) with Cs(+). Moreover, the extrapolated I(CCh) reversal shifted to approximately -20 mV on removal of 50% extracellular Na(+). These results are consistent with I(CCh) being a nonspecific cation current. Finally, noise analysis of I(CCh) returned an estimated conductance of the underlying channels of approximately 13.5 pS. We conclude that the depolarizing effect of muscarinic stimuli on entorhinal-cortex layer-II principal neurons depends on both the block of a K(+) conductance and the activation of a "noisy" nonspecific cation current. We suggest that the membrane current fluctuations brought about by I(CCh) channel noise may facilitate the "theta" oscillatory dynamics of these neurons and enhance firing reliability and synchronization.

Spike Patterning by Ca2+-dependent Regulation of a Muscarinic Cation Current in Entorhinal Cortex Layer II Neurons

Journal of Neurophysiology. Sep, 2004  |  Pubmed ID: 15152013

In entorhinal cortex layer II neurons, muscarinic receptor activation promotes depolarization via activation of a nonspecific cation current (I(NCM)). Under muscarinic influence, these neurons also develop changes in excitability that result in activity-dependent induction of delayed firing and bursting activity. To identify the membrane processes underlying these phenomena, we examined whether I(NCM) may undergo activity-dependent regulation. Our voltage-clamp experiments revealed that appropriate depolarizing protocols increased the basal level of inward current activated during muscarinic stimulation and suggested that this effect was due to I(NCM) upregulation. In the presence of low buffering for intracellular Ca(2+), this upregulation was transient, and its decay could be followed by a phase of I(NCM) downregulation. Both up- and downregulation were elicited by depolarizing stimuli able to activate voltage-gated Ca(2+) channels (VGCC); both were sensitive to increasing concentrations of intracellular Ca(2+)-chelating agents with downregulation being abolished at lower Ca(2+)-buffering capacities; both were reduced or suppressed by VGCC block or in the absence of extracellular Ca(2+). These data indicate that relatively small increases in [Ca(2+)](i) driven by firing activity can induce upregulation of a basal muscarinic depolarizing-current level, whereas more pronounced [Ca(2+)](i) elevations can result in I(NCM) downregulation. We propose that the interaction of activity-dependent positive and negative feedback mechanisms on I(NCM) allows entorhinal cortex layer II neurons to exhibit emergent properties, such as delayed firing and enhanced or suppressed responses to repeated stimuli, that may be of importance in the memory functions of the temporal lobe and in the pathophysiology of epilepsy.

Abolition of Spindle Oscillations and 3-Hz Absence Seizurelike Activity in the Thalamus by Using High-frequency Stimulation: Potential Mechanism of Action

Journal of Neurosurgery. Sep, 2005  |  Pubmed ID: 16235687

The mechanism of action whereby high-frequency stimulation (HFS) in the thalamus ameliorates tremor and epilepsy is unknown. The authors studied the effects of HFS on thalamocortical relay neurons in a ferret in vitro slice preparation to test the hypothesis that HFS abolishes synchronized oscillations by neurotransmitter release.

Effects of Serotonin on the Intrinsic Membrane Properties of Layer II Medial Entorhinal Cortex Neurons

Hippocampus. 2007  |  Pubmed ID: 17146777

Although serotonin (5-HT) is an important neuromodulator in the superficial layers of the medial entorhinal cortex (mEC), there is some disagreement concerning its influences upon the membrane properties of neurons within this region. We performed whole cell recordings of mEC Layer II projection neurons in rat brain slices in order to characterize the intrinsic influences of 5-HT. In current clamp, 5-HT evoked a biphasic response consisting of a moderately short latency and large amplitude hyperpolarization followed by a slowly developing, long lasting, and small amplitude depolarization. Correspondingly, in voltage clamp, 5-HT evoked a robust outward followed by a smaller inward shift of holding current. The outward current evoked by 5-HT showed a consistent current/voltage (I/V) relationship across cells with inward rectification, and demonstrating a reversal potential that was systematically dependent upon the extracellular concentration of K(+), suggesting that it was predominantly carried by potassium ions. However, the inward current showed a less consistent I/V relationship across different cells, suggesting multiple independent ionic mechanisms. The outward current was mediated through activation of 5-HT(1A) receptors via a G-protein dependent mechanism while inward currents were evoked in a 5-HT(1A)-independent fashion. A significant proportion of the inward current was blocked by the I(h) inhibitor ZD7288 and appeared to be due to 5-HT modulation of I(h) as 5-HT shifted the activation curve of I(h) in a depolarizing fashion. Serotonin is thus likely to influence, in a composite fashion, the information processing of Layer II neurons in the mEC and thus, the passage of neocortical information via the perforant pathway to the hippocampus.

Shining New Light on the Brain's "bilingual Signature": a Functional Near Infrared Spectroscopy Investigation of Semantic Processing

NeuroImage. Feb, 2008  |  Pubmed ID: 18054251

Decades of research have shown that, from an early age, proficient bilinguals can speak each of their two languages separately (similar to monolinguals) or rapidly switch between them (dissimilar to monolinguals). Thus we ask, do monolingual and bilingual brains process language similarly or dissimilarly, and is this affected by the language context? Using an innovative brain imaging technology, functional Near Infrared Spectroscopy (fNIRS), we investigated how adult bilinguals process semantic information, both in speech and in print, in a monolingual language context (one language at a time) or in a bilingual language context (two languages in rapid alternation). While undergoing fNIRS recording, ten early exposed, highly proficient Spanish-English bilinguals completed a Semantic Judgment task in monolingual and bilingual contexts and were compared to ten English monolingual controls. Two hypotheses were tested: the Signature Hypothesis predicts that early, highly proficient bilinguals will recruit neural tissue to process language differently from monolinguals across all language contexts. The Switching Hypothesis predicts that bilinguals will recruit neural tissue to process language similarly to monolinguals, when using one language at a time. Supporting the Signature Hypothesis, in the monolingual context, bilinguals and monolinguals showed differences in both hemispheres in the recruitment of DLPFC (BA 46/9) and IFC (BA 47/11), but similar recruitment of Broca's area (BA 44/45). In particular, in the monolingual context, bilinguals showed greater signal intensity in channels maximally overlaying DLPFC and IFC regions as compared to monolinguals. In the bilingual context, bilinguals demonstrated a more robust recruitment of right DLPFC and right IFC. These findings reveal how extensive early bilingual exposure modifies language organization in the brain-thus imparting a possible "bilingual signature." They further shed fascinating new light on how the bilingual brain may reveal the biological extent of the neural architecture underlying all human language and the language processing potential not fully recruited in the monolingual brain.

Stimulus-induced Changes in Blood Flow and 2-deoxyglucose Uptake Dissociate in Ipsilateral Somatosensory Cortex

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Dec, 2008  |  Pubmed ID: 19118167

The present study addresses the relationship between blood flow and glucose consumption in rat primary somatosensory cortex (SI) in vivo. We examined bilateral neuronal and hemodynamic changes and 2-deoxyglucose (2DG) uptake, as measured by autoradiography, in response to unilateral forepaw stimulation. In contrast to the contralateral forepaw area, where neuronal activity, blood oxygenation/flow and 2DG uptake increased in unison, we observed, in the ipsilateral SI, a blood oxygenation/flow decrease and arteriolar vasoconstriction in the presence of increased 2DG uptake. Laminar electrophysiological recordings revealed an increase in ipsilateral spiking consistent with the observed increase in 2DG uptake. The vasoconstriction and the decrease in blood flow in the presence of an increase in 2DG uptake in the ipsilateral SI contradict the prominent metabolic hypothesis regarding the regulation of cerebral blood flow, which postulates that the state of neuroglial energy consumption determines the regional blood flow through the production of vasoactive metabolites. We propose that other factors, such as neuronal (and glial) release of messenger molecules, might play a dominant role in the regulation of blood flow in vivo in response to a physiological stimulus.

Dual Language Use in Sign-speech Bimodal Bilinguals: FNIRS Brain-imaging Evidence

Brain and Language. May-Jun, 2009  |  Pubmed ID: 18976807

The brain basis of bilinguals' ability to use two languages at the same time has been a hotly debated topic. On the one hand, behavioral research has suggested that bilingual dual language use involves complex and highly principled linguistic processes. On the other hand, brain-imaging research has revealed that bilingual language switching involves neural activations in brain areas dedicated to general executive functions not specific to language processing, such as general task maintenance. Here we address the involvement of language-specific versus cognitive-general brain mechanisms for bilingual language processing. We study a unique population, bimodal bilinguals proficient in signed and spoken languages, and we use an innovative brain-imaging technology, functional Near-Infrared Spectroscopy (fNIRS; Hitachi ETG-4000). Like fMRI, the fNIRS technology measures hemodynamic change, but it is also advanced in permitting movement for unconstrained speech and sign production. Participant groups included (i) hearing ASL-English bilinguals, (ii) ASL monolinguals, and (iii) English monolinguals. Imaging tasks included picture naming in "Monolingual mode" (using one language at a time) and in "Bilingual mode" (using both languages either simultaneously or in rapid alternation). Behavioral results revealed that accuracy was similar among groups and conditions. By contrast, neuroimaging results revealed that bilinguals in Bilingual mode showed greater signal intensity within posterior temporal regions ("Wernicke's area") than in Monolingual mode. Significance: Bilinguals' ability to use two languages effortlessly and without confusion involves the use of language-specific posterior temporal brain regions. This research with both fNIRS and bimodal bilinguals sheds new light on the extent and variability of brain tissue that underlies language processing, and addresses the tantalizing questions of how language modality, sign and speech, impact language representation in the 7 brain.

At the Rhythm of Language: Brain Bases of Language-related Frequency Perception in Children

NeuroImage. Jan, 2012  |  Pubmed ID: 22230949

What neural mechanisms underlie language and reading acquisition? Slow rhythmic modulations in the linguistic stream (below 8Hz) mark syllable and word boundaries in the continuous linguistic stream, potentially helping children master the words and structures of their language. Converging evidence across language and reading research suggests that children's sensitivity to these slow rhythmic modulations is important for language and reading acquisition. In infancy, children produce rhythmically alternating syllables, or babbles, at a slow frequency of ~1.5Hz or 660ms (Petitto et al., 2001). In early grades, children's sensitivity to slow rhythmic modulations correlates with their reading ability (Goswami, 2011). We used functional Near Infrared (fNIRS) imaging to investigate the brain bases of "language rhythm" in beginning readers (ages 6-9). Right hemisphere showed an overall greater activation toward the slow rhythmic stimuli, and left hemisphere showed greater activation toward 1.5Hz, relative to faster and slower frequencies. The findings suggest that while right hemisphere might have an overall better ability to process rhythmic sensitivity, left hemisphere might have a select sensitivity to a preferred range of slow rhythmic modulations-a range that might be particularly salient to brain mechanisms responsible for cross-modal language processing and reading acquisition.

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