Thalamic Control of Layer 1 Circuits in Prefrontal Cortex

Abstract

Knowledge of thalamocortical (TC) processing comes mainly from studying core thalamic systems that project to middle layers of primary sensory cortices. However, most thalamic relay neurons comprise a matrix of cells that are densest in the “nonspecific” thalamic nuclei and usually target layer 1 of multiple cortical areas. A longstanding hypothesis is that matrix TC systems are crucial for regulating neocortical excitability during changing behavioral states, yet we know almost nothing about the mechanisms of such regulation. It is also unclear whether synaptic and circuit mechanisms that are well established for core sensory TC systems apply to matrix TC systems. Here we describe studies of thalamic matrix influences on mouse prefrontal cortex using optogenetic and in vitro electrophysiology techniques. Channelrhodopsin-2 was expressed in midline and paralaminar (matrix) thalamic neurons, and their layer 1-projecting TC axons were activated optically. Contrary to conventional views, we found that matrix TC projections to layer 1 could transmit relatively strong, fast, high-fidelity synaptic signals. Layer 1 TC projections preferentially drove inhibitory interneurons of layer 1, especially those of the late-spiking subtype, and often triggered feedforward inhibition in both layer 1 interneurons and pyramidal cells of layers 2/3. Responses during repetitive stimulation were far more sustained for matrix than for core sensory TC pathways. Thus, matrix TC circuits appear to be specialized for robust transmission over relatively extended periods, consistent with the sort of persistent activation observed during working memory and potentially applicable to state-dependent regulation of excitability.

Robustness of sensory-evoked excitation is increased by inhibitory inputs to distal apical tuft dendrites

“…Second, L1 is innervated by long-range pathways from multiple cortical (27) and thalamic areas (e.g., posterior medial division of the thalamus (POm) (28)), as well as from neuromodulatory pathways (29). We therefore suggest that L1 INs are primarily driven by nonspecific long-range pathways, for example as previously demonstrated by neurons in the contralateral hemisphere (6) or by thalamic nuclei (30). In line with this suggestion is our observation that whisker-evoked APs of L1 INs were largely unaffected by recurrent excitation in the underlying layers (10).…”

Synaptic Microcircuits in the Barrel Cortex

“…Given that interneurons comprise only 8.1 % (rat, Meyer et al 2011)or 8.5 % (mouse, [24]) of the total neuron population in layer 4 of the barrel cortex the number of TC afferents innervating L4 interneurons is relatively large [21]. A major group of L4 interneurons targeted by TC afferents are the so-called FS, PV + interneurons [131,[157][158][159]. They appear to be more readily recruited by TC input than excitatory neurons and are the major source of rapid intracortical inhibition in layer 4 [25,158,160,161] and the infragranular cortical layers (e.g.…”

“…Because VIP + L2/3 interneuron dendrites project into layer 1 they can be targeted by long-range axonal projections from other cortical areas and subcortical regions [159,[195][196][197]. Using an optogenetic approach, Lee and coworkers [189] were able to demonstrate that VIP + L2/3 interneurons receive strong input from the primary vibrissal motor cortex (vM1), while non-VIP + 5-HT 3a R + interneurons do not.…”

Determining Changes in Neural Circuits in Tuberous Sclerosis

“…Brain slice preparation, solutions, and recording conditions Cruikshank et al, 2010Cruikshank et al, , 2012 are provided in detail in the Supplemental Experimental Procedures. Data were collected with Clampex 10.0 and analyses were performed post hoc using Clampfit 10.0.…”

“…Slice Preparation: Brain sections were prepared from young mice (postnatal age: 20-23 days) of either sex as previously described Cruikshank et al, 2010;Cruikshank et al, 2012). Briefly, mice were deeply anesthetized with isofluorane, then decapitated.…”