Behavioral state-dependent modulation of distinct interneuron subtypes and consequences for circuit function

Abstract

Multiple neuromodulators regulate neuronal response properties and synaptic connections in order to adjust circuit function. Inhibitory interneurons are a diverse group of cells that are differentially modulated depending on neuronal subtype and play key roles in regulating local circuit activity. Importantly, new tools to target specific subtypes are greatly improving our understanding of interneuron circuits and their modulation. Indeed, recent work has demonstrated that during different behavioral states interneuron activity changes in a subtype specific manner in both neocortex and hippocampus. Furthermore, in neocortex, modulation of specific interneuron microcircuits results in pyramidal cell disinhibition with important consequences for synaptic plasticity and animal behavior. Thus, neurmodulators tune the output of different interneuron subtypes to provide neural circuits with great flexibility.

Molecular mechanisms of epilepsy

“…For example, if transient imbalances in inhibition and excitation engendered further imbalance, this imbalance could occasionally build to the point of engendering a seizure. Activity-dependent reductions in the efficacy of neuronal inhibition, or activity-dependent disinhibition, comprises one such mechanism, or set of mechanisms 24, 25, 26 . If disinhibition occurred only at extremes of local network activity, then the probability of ictal transition would depend on the probability of that exceptional level of local network activity.…”

Neural control of brain state

“…Both cholinergic and serotoninergic systems, for example, can activate rapid excitatory postsynaptic potentials in postsynaptic targets through nicotinic and 5HT 3A receptors, respectively [44–46] (see also Higley and Picciotto in this issue [83]). In cortical networks, these receptors are often (but not exclusively) located on particular subpopulations of GABAergic interneurons [47,48] (see also Wester and McBain in this issue [84]) and considerable effort has been recently applied to understand the roles of these pathways (see below).…”

Motivated state control in larval zebrafish: behavioral paradigms and anatomical substrates

“…Motivational states reflect the activity of neuromodulatory systems that shape the activity of neuronal circuits over timeframes of minutes to hours (Pfaff et al, 2008). Neuromodulation has been extensively studied at molecular and cellular levels in many systems revealing that amines, neuropeptides and small molecules powerfully influence the activity and output of neurons in most brain regions (Marder and Calabrese, 1996; Marder, O’Leary and Shruti, 2014; Wester and McBain, 2014). Many neuromodulators act broadly, allowing coordinated tuning of disparate circuits and providing flexibility in the function of groups of neurons as computational needs change (Robbins, 1997).…”