Fast Synaptic Subcortical Control of Hippocampal Circuits

Abstract

Cortical information processing is under state-dependent control of subcortical neuromodulatory systems. Although this modulatory effect is thought to be mediated mainly by slow nonsynaptic metabotropic receptors, other mechanisms, such as direct synaptic transmission, are possible. Yet, it is currently unknown if any such form of subcortical control exists. Here, we present direct evidence of a strong, spatiotemporally precise excitatory input from an ascending neuromodulatory center. Selective stimulation of serotonergic median raphe neurons produced a rapid activation of hippocampal interneurons. At the network level, this subcortical drive was manifested as a pattern of effective disynaptic GABAergic inhibition that spread throughout the circuit. This form of subcortical network regulation should be incorporated into current concepts of normal and pathological cortical function.

Neurodevelopment, GABA System Dysfunction, and Schizophrenia

“…PV þ cells are fast-spiking basket and chandelier cells that innervate pyramidal cell soma and axon initial segments, respectively (Markram et al, 2004), as well as other interneuron populations (Lovett-Barron et al, 2012). Another type of basket cells, containing CCK, also form perisomatic contacts onto pyramidal cells; however, they are distinguished from the PV þ variety by their slower, accommodating firing patterns (Hefft and Jonas, 2005) that integrate neuromodulatory information with faster network activity (Freund, 2003;Varga et al, 2009). Interconnected networks of NPY þ neurogliaform cells mediate regional tonic inhibition through extrasynaptic volume transmission in multiple cortical and subcortical regions (Manko et al, 2012;Olah et al, 2009;Price et al, 2005).…”

Targeting brain serotonin synthesis: insights into neurodevelopmental disorders with long-term outcomes related to negative emotionality, aggression and antisocial behaviour

“…Tph2 2/2 mice also displayed elevated concentrations of GABA in the hippocampus, with a trend towards reduced PV-specific neuron numbers in the CA3 region of the dorsal hippocampus, whereas volume, total number and density of interneurons remain unaffected. Selective activation of MnR 5-HT neurons has been reported to directly activate dorsal hippocampal interneurons [112], leading to an overall inhibition of the hippocampal formation. Dense innervations of the MnR originating beaded serotonergic axons with large spherical varicosities and fine DR axons can be found in the dorsal hippocampus [113,114].…”

Serotonin Modulates Fast-Spiking Interneuron and Synchronous Activity in the Rat Prefrontal Cortex through 5-HT1Aand 5-HT2AReceptors

“…Because the medial PFC projects densely to the DRN, this response may be due to feedforward inputs from cortico-raphe pyramidal neurons activated antidromically from the DRN . Alternatively, a glutamatergic response induced by 5-HT/glutamate corelease from serotonergic terminals should also be considered (Varga et al, 2009). This unit was confirmed to be PV positive.…”