Core Differences in Synaptic Signaling Between Primary Visual and Dorsolateral Prefrontal Cortex

Abstract

Neurons in primary visual cortex (V1) are more resilient than those in dorsolateral prefrontal cortex (dlPFC) in aging, schizophrenia and Alzheimer’s disease. The current study compared glutamate and neuromodulatory actions in macaque V1 to those in dlPFC, and found striking regional differences. V1 neuronal firing to visual stimuli depended on AMPA receptors, with subtle NMDA receptor contributions, while dlPFC depends primarily on NMDA receptors. Neuromodulatory actions also differed between regions. In V1, cAMP signaling increased neuronal firing, and the phosphodiesterase PDE4A was positioned to regulate cAMP effects on glutamate release from axons. HCN channels in V1 were classically located on distal dendrites, and enhanced cell firing. These data contrast with dlPFC, where PDE4A and HCN channels are concentrated in thin spines, and cAMP-HCN signaling gates inputs and weakens firing. These regional differences may explain why V1 neurons are more resilient than dlPFC neurons to the challenges of age and disease.

Alzheimer’s-like pathology in aging rhesus macaques: Unique opportunity to study the etiology and treatment of Alzheimer’s disease

“…V1 neurons are especially reliant on AMPAR rather than NMDAR neurotransmission (36), and show beneficial effects of cAMP signaling, where PKA increases sensory-evoked firing, consistent with cAMP-related proteins positioned to enhance glutamate release in axon terminals (36). These experiments also showed classic location and function of hyperpolarization-activated cyclic nucleotide (HCN) channels on the distal apical dendrite, where blockade reduced neuronal firing (36).…”

“…Studies of V1 in rhesus monkeys show classic neurotransmission and neuromodulatory mechanisms (Fig. 3A) (36). V1 neurons are especially reliant on AMPAR rather than NMDAR neurotransmission (36), and show beneficial effects of cAMP signaling, where PKA increases sensory-evoked firing, consistent with cAMP-related proteins positioned to enhance glutamate release in axon terminals (36).…”

“…(B) In contrast to V1, layer III dlPFC NMDAR synapses on spines express feedforward, calcium-cAMP-K + channel signaling, which reduces firing. Reprinted from ref 36,. by permission of Oxford University Press.…”

Distinct properties of layer 3 pyramidal neurons from prefrontal and parietal areas of the monkey neocortex

“…Within this network, sensory and association 63 areas display different activity patterns during working memory tasks, reflecting the 64 transformation of sensory input into a behavioral response across a delay (Christophel et al, 65 2017). For example, neurons in primary visual cortex (V1) increase their firing rate during 66 stimulus presentation, whereas neurons in the dorsolateral prefrontal cortex (DLPFC) often 67 change their activity during the delay period (Dotson et al, 2018;Yang et al, 2018;Quentin et 68 al., 2019). These regional differences might reflect the hierarchy of activity timescales observed 69 in the primate neocortex (Murray et al, 2014).…”

Distinct Properties of Layer 3 Pyramidal Neurons from Prefrontal and Parietal Areas of the Monkey Neocortex

“…Within this network, sensory and association areas display different activity patterns during working memory tasks, reflecting the transformation of sensory input into a behavioral response across a delay (Christophel et al, 2017). For example, neurons in primary visual cortex (V1) increase their firing rate during stimulus presentation, whereas neurons in the dorsolateral PFC (DLPFC) often change their activity during the delay period (Dotson et al, 2018;Yang et al, 2018;Quentin et al, 2019). These regional differences might reflect the hierarchy of activity timescales observed in the primate neocortex (Murray et al, 2014).…”