Prelimbic cortical targets of ventromedial thalamic projections include inhibitory interneurons and corticostriatal pyramidal neurons in the rat

Abstract

Ventromedial thalamic axons innervate cortical layer I and make contacts onto the apical dendritic tuft of pyramidal neurons. Optical stimulation of ventromedial thalamic axon terminals in prefrontal cortical areas in mouse brain slices evokes responses in corticocortical, corticothalamic and layer I inhibitory interneurons. Using anterograde tracing techniques and immunohistochemistry in male Sprague-Dawley rats, we provide anatomical evidence that ventromedial thalamic axon terminals in prelimbic cortex make contacts onto pyramidal neurons and, in particular, onto corticostriatal neurons as well as layer I inhibitory interneurons. Using stereology, we made quantitative estimates of contacts in uppermost prelimbic layer I onto dendrites of pyramidal neurons, corticostriatal neurons and layer I inhibitory interneurons. Prefrontal cortex has long been associated with decision making. Specifically, corticostriatal neurons in rat prelimbic cortex play an important role in cost-benefit decision making. Although recent experiments have detailed the physiology of this area in thalamocortical circuits, the extent of the impact of ventromedial thalamic input on corticostriatal neurons or layer I inhibitory interneurons has not been explored. Our quantitative anatomical results provide evidence that most ventromedial thalamic input to pyramidal neurons is provided to corticostriatal neurons and that overall more contacts are made onto the population of excitatory than onto the population of inhibitory neurons.

Distinct fastigial output channels and their impact on temporal lobe seizures

“…As such, other areas FN-CL neurons project to, including the VM nucleus of the thalamus, may contribute to the anti-seizure effects shown here. The VM projects to cortical areas including anterolateral motor cortex (Guo et al, 2018) and infralimbic prefrontal cortex (Sieveritz and Arbuthnott, 2020), and can target inhibitory neurons (and in particular, layer 1 neurogliaform cells) (Armstrong et al, 2012;Overstreet-Wadiche and McBain, 2015;Anastasiades et al, 2021). Given the potential interest of basal ganglia circuitry to seizures (Iadarola and Gale, 1982;Garant and Gale, 1987;Wicker et al, 2019), it is also of interest that the VM receives inhibitory input from pars reticulata (Kase et al, 2015).…”

Ventral motor thalamic input to prelimbic cortex mediates cost-benefit decision-making in rats

“…We previously proposed that MT input regulates the activity of prelimbic layer 1 inhibitory interneurons. We further proposed that, in turn, layer 1 inhibitory interneurons regulate a network of cortical inhibitory interneurons, which ultimately regulates the activity of deep layer pyramidal neurons (Sieveritz and Arbuthnott, 2020) -26-To test our prediction, we stimulated MT and simultaneously inhibited layer 1 inhibitory interneurons using optogenetics. In three 9-to 10-week-old Sprague-Dawley rats, we placed small unilateral injections of 10-20 nl AAV5-CAG-ArchT-GFP in prelimbic cortical layer 1.…”

“…The ventromedial thalamus, one of the nuclei that make up MT, provides input to both prelimbic pyramidal neurons and prelimbic layer 1 inhibitory interneurons (Sieveritz and Arbuthnott, 2020). Hence, we were interested in whether prelimbic layer 1 inhibitory interneurons contribute to MT-mediated regulation of neuronal activity in deep layers of prelimbic cortex.…”

“…We previously proposed that MT input regulates the activity of prelimbic layer 1 inhibitory interneurons. We further proposed that, in turn, layer 1 inhibitory interneurons regulate a network of cortical inhibitory interneurons, which ultimately regulates the activity of deep layer pyramidal neurons (Sieveritz and Arbuthnott, 2020).…”

“…Our third and fourth experiment investigated a potential mechanism to explain how optogenetic inhibition of MT input to prelimbic cortex might induce the observed bias in cost-benefit decision-making. MT provides input to prelimbic pyramidal neurons and prelimbic layer 1 inhibitory interneurons (Collins et al, 2018; Sieveritz and Arbuthnott, 2020). Layer 1 inhibitory interneurons, in turn, inhibit a network of cortical inhibitory interneurons (Cruikshank et al, 2012), which regulates the activity of deep layer pyramidal neurons (Jiang et al, 2013; Lee et al, 2015).…”