Cell-Type Specificity of Callosally Evoked Excitation and Feedforward Inhibition in the Prefrontal Cortex

Abstract

SUMMARY Excitation and inhibition are highly specific in the cortex, with distinct synaptic connections made onto subtypes of projection neurons. The functional consequences of this selective connectivity depend on both synaptic strength and the intrinsic properties of targeted neurons but remain poorly understood. Here, we examine responses to callosal inputs at cortico-cortical (CC) and cortico-thalamic (CT) neurons in layer 5 of mouse prelimbic prefrontal cortex (PFC). We find callosally evoked excitation and feedforward inhibition are much stronger at CT neurons compared to neighboring CC neurons. Elevated inhibition at CT neurons reflects biased synaptic inputs from parvalbumin and somatostatin positive interneurons. The intrinsic properties of postsynaptic targets equalize excitatory and inhibitory response amplitudes but selectively accelerate decays at CT neurons. Feedforward inhibition further reduces response amplitude and balances action potential firing across these projection neurons. Our findings highlight the synaptic and cellular mechanisms regulating callosal recruitment of layer 5 microcircuits in PFC.

Mediodorsal and ventromedial thalamus engage distinct L1 circuits in the prefrontal cortex

“…VM inputs activate NDNF+ cells, which subsequently mediate thalamus-evoked inhibition of the local network. We previously found that PT cells receive much stronger inhibition from PV+ and SOM+ cells (Anastasiades et al, 2018a). Here we find NDNF+ cells also make stronger connections onto PT cells, suggesting this is a general property.…”

“…S4). We then injected AAV-DIO-ChR2-mCherry into the PFC and recorded light-evoked IPSCs from L2/3 interneurons or PYRs in the presence of TTX and 4-AP (Anastasiades et al, 2018a;Petreanu et al, 2009) (Fig. 4A-B).…”

“…L5 pyramidal cells segregate into pyramidal tract (PT) and intratelencephalic (IT) cells, which possess distinct properties (Harris and Shepherd, 2015). For example, the strength of excitatory inputs from thalamus and inhibitory inputs from PV+ and SOM+ cells differ at PT and IT cells (Anastasiades et al, 2018a;Collins et al, 2018;Crandall et al, 2017;Hilscher et al, 2017). To test if this is also true for connections from NDNF+ cells, we recorded from triplets of retrogradely-labeled PT and IT cells, as well as unlabeled PYR cells ( Fig.…”

“…Optogenetics. Glutamate release was triggered by activating channelrhodopsin-2 (ChR2) present in presynaptic terminals of either thalamic inputs to the PFC, or local circuit interneurons as previously described (Anastasiades et al, 2018a;Little and Carter, 2013). ChR2 was activated Pulses were delivered at 1 Hz using a pseudo-random 10 x 10 grid pattern, yielding an effective mapping area of 750 µm x 750 µm.…”

Ventral hippocampal projections to the medial prefrontal cortex regulate social memory

“…Coherent, synchronous oscillations between the vHIP and the mPFC underlie working memory tasks in rats (Gordon, 2011). Entrainment of these oscillations occurs in the first postnatal week (Brockmann et al, 2013) and is driven by monosynaptic glutamatergic projections from pyramidal neurons of the ventral CA1 and subiculum to pyramidal neurons and GABAergic interneurons in the IL and PL subregions of the mPFC (Anastasiades et al, 2018;Dégenètais et al, 2003;Dembrow et al, 2010;Thierry et al, 2000). Despite the wealth of information linking this projection to neuropsychiatric disorders (Li et al, 2015), little is known about the synaptic and cellular bases of this long-range projection.…”