Spiny neurons of amygdala, striatum, and cortex use dendritic plateau potentials to detect network UP states

Abstract

Spiny neurons of amygdala, striatum, and cerebral cortex share four interesting features: (1) they are the most abundant cell type within their respective brain area, (2) covered by thousands of thorny protrusions (dendritic spines), (3) possess high levels of dendritic NMDA conductances, and (4) experience sustained somatic depolarizations in vivo and in vitro (UP states). In all spiny neurons of the forebrain, adequate glutamatergic inputs generate dendritic plateau potentials (“dendritic UP states”) characterized by (i) fast rise, (ii) plateau phase lasting several hundred milliseconds, and (iii) abrupt decline at the end of the plateau phase. The dendritic plateau potential propagates toward the cell body decrementally to induce a long-lasting (longer than 100 ms, most often 200–800 ms) steady depolarization (∼20 mV amplitude), which resembles a neuronal UP state. Based on voltage-sensitive dye imaging, the plateau depolarization in the soma is precisely time-locked to the regenerative plateau potential taking place in the dendrite. The somatic plateau rises after the onset of the dendritic voltage transient and collapses with the breakdown of the dendritic plateau depolarization. We hypothesize that neuronal UP states in vivo reflect the occurrence of dendritic plateau potentials (dendritic UP states). We propose that the somatic voltage waveform during a neuronal UP state is determined by dendritic plateau potentials. A mammalian spiny neuron uses dendritic plateau potentials to detect and transform coherent network activity into a ubiquitous neuronal UP state. The biophysical properties of dendritic plateau potentials allow neurons to quickly attune to the ongoing network activity, as well as secure the stable amplitudes of successive UP states.

Contribution of extrasynapticN-methyl-d-aspartate and adenosine A1 receptors in the generation of dendritic glutamate-mediated plateau potentials

“…(b) Adenosine A1 receptor (i) Source of adenosine During dendritic UP states [1,15], glutamate spillover leads to the activation of metabotropic glutamate receptors on glial cells [38]. The ensuing intracellular accumulation of Ca 2þ in glial processes causes a vesicular release of ATP in the extracellular milieu [39][40][41].…”

“…The proposed A1 receptor-mediated purinergic modulation of dendritic excitability depends on the coincidence of adenosine release and membrane depolarization (figure 3b). As strong glutamatergic inputs trigger (i) dendritic UP states [1,15] and (ii) ATP/adenosine release [41,75,76], the purinergic modulation of dendritic excitability will be spatially and temporally restricted to dendrites experiencing dendritic UP states. The results of this study show that blockade of adenosine A1 receptors removes the suppressing effects of dendritic K þ current thus extending the dendritic depolarization, as well as the associated calcium influx in the specific input-receiving dendrite.…”

Calcium regulation of HCN channels supports persistent activity in a multiscale model of neocortex

“…Additionally, we of course left out many unimportant features, a key role of modeling being to eventually determine which are the important and which the unimportant parameters related to a given functional outcome. Additional features that would be valuable to more fully understand persistent activity include I CAN cationic currents (Egorov et al, 2002, Tiganj et al, 2015), persistent sodium channels (Oikonomou et al, 2014, Zhou et al, 2015), and neuromodulatory synaptic receptors such as acetylcholine and dopamine (Sawaguchi and Goldman-Rakic, 1991, Sidiropoulou et al, 2009). A further omitted feature that is believed to be important is the aforementioned distribution of HCN isoforms by cell type and location.…”

“…Persistent neuronal activity, lasting several seconds, has been proposed to underlie several functions in the central nervous system including short term working memory (Goldman-Rakic, 1995, Braver et al, 1997, Kane and Engle, 2002) and motor preparatory set (Ames et al, 2014). Additional functions probably also depend on similar mechanisms subserved by the “UP state,” identified originally in sleep and in slice but now also demonstrated in visual cortex (Cossart et al, 2003) and other brain areas (Oikonomou et al, 2014, Zhou et al, 2015, Poskanzer and Yuste, 2011, Major and Tank, 2004). Computational models of network persistent activity that have been proposed largely rely on continued interactions of neurons maintaining activity in one another through mutual synaptic activation (Lim and Goldman, 2013, Lim and Goldman, 2014, Lisman et al, 1998, Wang, 1999a, Wang, 2001).…”

Rebuilding a realistic corticostriatal “social network” from dissociated cells

“…We are working on methods to identify individual pairs of synaptically connected cortical and striatal neurons to examine the properties of individual contacts. Nevertheless we do have MEA recordings whose analyses will generate testable predictions about the real brain, as well as a plausible explanation for the generation of “up” states in cultures and slices (Garcia-Munoz et al, 2015 ) that may be important in other areas of brain (Oikonomou et al, 2014 ).…”