Diversity in the Neuronal Machine

“Given such input variations, and the high heterogeneity of both cellular and synaptic properties in interneurons (887), how can synchronous oscillations be maintained robustly? Modeling studies suggest that synchrony can be more robustly realized in spite of heterogeneity when GABAA receptor-mediated synaptic inhibiti…”

“There are many different families of interneurons in the cortex (Freund and Buzs aki, 1996; Hippocampus McBain and Fisahn, 2001; Solt esz, 2005; Klausberger and Somogyi, 2008; Fishell and Rudy, 2011; Kepecs and Fishell, 2014) and hippocampal interneurons show diverse firing patterns during SPW-Rs from potent increase…”

“What has emerged are parallel systems of technique-specific, or even practitioner-specific, classifications, each based on a limited set of features, and which are nearly impossible to reconcile with each other (Soltesz, 2005).”

“Given the remarkable diversity of interneurons (Soltesz, 2006), we do not intend Hippocampus for this average to characterize any particular interneuron in the CA1.”

“In particular, it is unclear what the nature of the relationship is between heterogeneity of PCs (Bannister and Larkman, 1995; Mizuseki et al., 2011; Deguchi et al., 2011; Graves et al., 2012) and the well-known diversity of local GABAergic hippocampal interneurons (Soltesz, 2005).”

“…neuron specificity (Beierlein et al. 2003; Koester and Johnston 2005; Kozloski et al. 2001; Markram et al. 1998; Reyes et al. 1998) as earlier described for interneurons in neocortex and hippocampus (reviewed by Freund and Buzsáki 1996; Somogyi et al. 1998; Markram et al. 2004; Soltesz 2006).”

“We included eight model interneuron types (Klausberger and Somogyi, 2008; Soltesz, 2006; Armstrong and Soltesz, 2012): PV+ basket cells (these fast-spiking cells synapse on the somata and proximal dendrites of CA1 pyramidal cells), cholecystokinin+ (CCK+) basket cells (these regular-spiking cells…”

“stratum radiatum do not comprise the whole phenotypic spectrum of CCK+ interneurons (Soltesz, 2005; Somogyi & Klausberger, 2005), they form a relatively homogeneous group of cells that allowed us to obtain connected pairs.”

“INTRODUCTION Neurons in the mammalian brain are highly heterogeneous (Soltesz, 2005; Marder and Goaillard, 2006) and show diverse responses to sensory stimuli and other events.”

“The spatio-temporal control of principal cell assemblies during endogenous brain rhythms is orchestrated by GABAergic interneurons (Soltesz, 2006; Somogyi et al., 2014).”

“Several of our non-GIN cell sample resembled a “fastspiking” (FS) interneuron profile (Cesare et al., 1996; Soltesz, 2006; Hu et al., 2010), including brief spike half-widths (<0.7 ms) and minimal spike frequency adaptation during long step current stimuli (>0.85 frequency adaptation ratio).”

“…interneurons are heterogeneous, with subpopulations distinguished by particular combinations of morphological, physiological, and molecular attributes (Cauli et al. 1997;Kawaguchi andKubota 1997;McBain and Fisahn 2001) and with variance in these attributes within subpopulations (Soltesz 2006).”

“Approximately 10--20% are nonpyramidal c-aminobutyric acidergic (GABAergic) neurons that evoke chloride-mediated, inhibitory postsynaptic potentials (IPSPs; Jones 1975; Houser et al. 1983; Beaulieu et al. 1992; for a review, see Soltesz 2006).”

“However, understanding cortical inhibition has been a challenging task as this process is executed through a diverse group of local and long-range projecting (LRP) GABAergic neurons (Soltesz, 2006).”

“…membrane time constants, and inputs from several modulatory subcortical sources, are thought of as a \fine-tuning," highly plastic system that is more prone to both short-term and long-term modulatory influences (Freund, 2003; Glickfeld and Scanziani, 2006; Soltesz, 2006; Freund and Katona, 2007).”

“Nevertheless, these neurons are highly diverse and therefore notoriously difficult to classify (e.g., Somogyi et al. 1998; Soltesz 2006; Ascoli et al. 2008).”

“The hippocampus contains multiple classes of interneurons with different functions; immunostaining for neuropeptides provides a means of distinguishing among the classes (Freund and Buzsaki, 1996; Soltesz, 2006).”

“Cellular heterogeneity characterizes the organization of the cerebral cortex, where functionally and structurally distinct classes of neurons mediate specific aspects of information processing (Markram et al., 2004; Soltesz, 2005).”

“We propose that this variability has biological significance (Soltesz, 2006) and generates stability of firing within the Imp cell population.”

“This structure is populated by a high diversity of local-circuit and long-range projecting (LRP) GABAergic neurons, which play highly specialized roles in coordinating different computations carried out by principal cells (PCs) (Soltesz 2006; Klausberger and Somogyi 2008; Pelkey et al. 2017).”

“Because the cannabinoid CB1 receptor is localized to the axons of the subset of perisomatically targeting basket cells that contain the neuropeptide cholecystokinin or CCK (Freund 2003; Soltesz 2005) (Fig.”

“interneuron innervate pyramidal cells, targeting different cellular compartments (Buhl et al. 1994; Halasy, 1996; Somogyi & Klausberger, 2005; Soltesz, 2006).”

“Each population of neurons plays a unique role in the circuitry (Bezaire et al., 2016; Pelkey et al., 2017; Roux and Buzsáki, 2015; Soltesz, 2006), and together, they allow for the emergent functionality of the hippocampus, including effective navi- gation through time and space (Eichenbaum, 2014)…”

“Compared with principal cells, GABAergic INs exhibit specific dendritic and axonal organization, intrinsic biophysical and synaptic properties, network activity, and brain-state-dependent firing behaviour (Freund & Buzsaki, 1996; McBain & Fisahn, 2001; Soltesz, 2006; Klausberger & Somogyi, 2008).”

“Even if a single population of cells could be targeted, neuronal populations have variable properties and manipulating a population essentially averages diverse functional effects (see Soltesz 2006).”

“characteristics confer PV neurons the ability to synchronize the activities of pyramidal neural networks (30, 31).”

“Frontiers in Psychology 06 frontiersin.org acceptable approach providing that we appreciate that this may remove functionally-relevant variability (Parra et al., 1998; Aradi and Soltesz, 2002; Golowasch et al., 2002; Soltesz, 2006; Parker and Srivastava, 2013).”

“Inhibitory neurons in the cerebral cortex are morphologically, neurochemically, physiologically and thereby functionally diverse, with different subsets of these neurons regulating distinct aspects of information processing (Buzsaki, 2006; Markram et al., 2004; Soltesz, 2005; Wang et al., 2004).”

“Many of these properties covary, indicating that the heterogeneity found in pyramidal neurons is not due to random events but instead due to their separation into specific cellular subtypes [6] that is choreographed by transcriptional regulation during neuronal development [7].”

“While variability is gradually being recognized (see Soltesz, 2006), its nature and relevance remain unclear at the neuronal or network level.”

“Synaptic Variability Introduces State-Dependent Modulation of”

“Understanding the rules of local circuits with inhibitory and excitatory components is particularly challenging given the notable the diversity of interneuron cell types and connectivity motifs in the brain (Soltesz, 2006; Soltesz & Losonczy, 2018).”

“…the relative abundance of inhibitory interneurons is higher than in rodents, and this is highest in higher-order associative areas such as the human prefrontal cortex, possibly reflecting enhanced demands for cognitive processing (Soltesz, 2006; Kooijmans et al., 2020; Hanson et al., 2025).”

“The firing properties of neurons depend critically on neuron type [11], brain structure [12], brain state [13], arousal [14], and other factors.”

“Although there is no general agreement on what is required to define a neuronal population as a subtype or “species” (Soltesz, 2005), the extent of the differentially expressed properties we observed approaches the requirements of some recently proposed definitions (Migliore and Shepherd, 2005; Somogyi and Klausberger…”