On how correlations between excitatory and inhibitory synaptic inputs maximize the information rate of neuronal firing

Cortical neurons receive barrages of excitatory and inhibitory inputs which are not independent, as network structure and synaptic kinetics impose statistical correlations. Experiments in vitro and in vivo have demonstrated correlations between inhibitory and excitatory synaptic inputs in which inhibition lags behind excitation in cortical neurons. This delay arises in feed-forward inhibition circuits and ensures that coincident excitation and inhibition do not preclude neuronal firing. Conversely, inhibition that is too delayed broadens neuronal integration times, thereby diminishing spike-time precision and increasing the firing frequency. This led us to hypothesize that the correlation between excitatory and inhibitory synaptic inputs modulates the encoding of information of neural spike trains. We tested this hypothesis by investigating the effect of such correlations on the information rate (IR) of spike trains using the Hodgkin-Huxley model in which both synaptic and membrane conductances are stochastic. We investigated two different synaptic input regimes: balanced synaptic conductances and balanced currents. Our results show that correlations arising from the synaptic kinetics, tau, and millisecond lags, delta, of inhibition relative to excitation strongly affect the IR of spike trains. In the regime of balanced synaptic currents, for short time lags (delta ~ 1 ms) there is an optimal tau that maximizes the IR of the postsynaptic spike train. Given the short time scales for monosynaptic inhibitory lags and synaptic decay kinetics reported in cortical neurons under physiological contexts, we propose that feed-forward inhibition in cortical circuits is poised to maximize the rate of information transfer between cortical neurons. Our results also provide a possible explanation for how certain drugs and genetic mutations affecting the synaptic kinetics can deteriorate information processing in the brain

Dopaminergic signals for reward, performance and social outcomes dynamically re-tune during courtship

Hunger, thirst, loneliness and ambition determine the reward value of food, water, social interaction, and performance outcome. Dopamine (DA) neurons respond to rewards meeting these diverse needs, but it remains unclear how behavior and DA signals change as priorities change with new opportunities in the environment. One possibility is that DA signals for distinct drives are routed to distinct DA pathways. Another possibility is that DA signals in a given pathway are dynamically tuned to rewards set by the current priority. Here we used electrophysiology and fiber photometry to test how DA signals associated with quenching thirst, singing a good song, and courting a mate change as thirsty, lonely, and sexually motivated male songbirds were provided with opportunities to retrieve water, evaluate song performance, or court a female. When alone, water reward signals were observed in two mesostriatal pathways but singing-related performance error signals were routed to Area X, a striatal nucleus specialized for singing. When courting a female, the expression of thirst was reduced and DA responses to both water and song performance outcomes diminished. Instead, DA signals in Area X were driven by female calls timed with the courtship song. Thus the DA system handled coexisting drives in two ways: by routing vocal performance and social feedback signals to a striatal area for communication, and by flexibly re-tuning to rewards set by the prioritized drive

Parvalbumin interneuron mediated feedforward inhibition controls signal output in the deep layers of the perirhinal-entorhinal cortex

The perirhinal (PER) and lateral entorhinal (LEC) cortex form an anatomical link between the neocortex and the hippocampus. However, neocortical activity is transmitted through the PER and LEC to the hippocampus with a low probability, suggesting the involvement of the inhibitory network. This study explored the role of interneuron mediated inhibition, activated by electrical stimulation in the agranular insular cortex (AiP), in the deep layers of the PER and LEC. Activated synaptic input by AiP stimulation rarely evoked action potentials in the PER-LEC deep layer excitatory principal neurons, most probably because the evoked synaptic response consisted of a small excitatory and large inhibitory conductance. Furthermore, parvalbumin positive (PV) interneurons - a subset of interneurons projecting onto the axo-somatic region of principal neurons - received synaptic input earlier than principal neurons, suggesting recruitment of feedforward inhibition. This synaptic input in PV interneurons evoked varying trains of action potentials, explaining the fast rising, long lasting synaptic inhibition received by deep layer principal neurons. Altogether, the excitatory input from the AiP onto deep layer principal neurons is overruled by strong feedforward inhibition. PV interneurons, with their fast, extensive stimulus-evoked firing, are able to deliver this fast evoked inhibition in principal neurons. This indicates an essential role for PV interneurons in the gating mechanism of the PER-LEC network

Serotonin in seizures and epilepsy: a neurodevelopmental perspective

The term epilepsy refers to a diverse group of disorders of different origin, which are all characterized by the repeated occurrence of transitory and localized outbursts of electrical activity, known as seizures. Several forms of epilepsy have a clear neurodevelopmental origin, due to congenital brain malformations, altered neurotransmission, or defects in maturation and plasticity of neuronal networks. A role for serotonin (5-hydroxytryptamine, 5-HT) in epilepsy has long been proposed, and classical pharmacological studies provided contrasting evidences about the 5-HT receptor pathways involved in epilepsy, supporting both a pro- and an antiepileptic action of 5-HT. More recently, work performed on mice lacking genes involved in 5-HT neuron differentiation showed that an altered development of 5-HT circuits markedly affects neuronal activity in postnatal life, indicating a protective role of 5-HT against hyperexcitability. In this chapter, we will review the major developmental perturbations of 5-HT innervation affecting neuronal excitability and seizure susceptibility