Inhibitory interneurons in visual cortical plasticity

Abstract

For proper maturation of the neocortex and acquisition of specific functions and skills, exposure to sensory stimuli is vital during critical periods of development when synaptic connectivity is highly malleable. To preserve reliable cortical processing, it is essential that these critical periods end after which learning becomes more conditional and active interaction with the environment becomes more important. How these age-dependent forms of plasticity are regulated has been studied extensively in the primary visual cortex. This has revealed that inhibitory innervation plays a crucial role and that a temporary decrease in inhibition is essential for plasticity to take place. Here, we discuss how different interneuron subsets regulate plasticity during different stages of cortical maturation. We propose a theory in which different interneuron subsets select the sources of neuronal input that undergo plasticity.

Keywords: Adult; Inhibition V1; Neurogliaform cells; Ocular dominance plasticity; Parvalbumin; Perceptual learning; Somatostatin; Vasoactive intestinal peptide.

Fig. 1

Anatomy of the embryonic telencephalon showing the two main structures from which inhibitory interneurons are derived: the medial ganglionic eminence (MGE) and the caudal ganglionic eminence (CGE), as a 3D structure in the intact brain as well as in two sections. The MGE and CGE give rise to different interneuron subtypes: 5HT3aR expressing interneurons are derived from the CGE and PV and SST expressing interneurons are derived from the MGE. Progenitor cells tangentially migrate to the appropriate cortical area before they radially position themselves via the ventricular zone (VZ), intermediate zone (IZ) and subplate (SP) to their final laminar position in the cortical plate (CP)

Fig. 2

Schematic representation of the main projections to and from pyramidal cells and interneurons within the six layers of the primary visual cortex (V1). Shown are rough estimates of densities (black circles) from local, thalamic (lateral geniculate nucleus (LGN) and the lateral posterior nucleus (LPN) of the thalamus), feedback and callosal projections to the different layers of V1 (left panel) and to different subtypes of interneurons (right panel). Estimates are based on the literature and Allen Mouse Brain Connectivity Atlas [158]. Layers 5 and 2/3 mainly receive local inputs, whereas layer 4 mostly receives thalamic input from the LGN. Conversely, layer 1 mostly receives thalamic input from the LPN, callosal inputs, and feedback projections. The subtypes of interneurons discussed in this article (middle right panel) express either a combination of the serotonin receptor 5HT3aR with reelin or vasoactive intestinal peptide (VIP) or are positive for parvalbumin (PV) or somatostatin (SST). Neurogliaform cells (NGF) express 5HT3aR and reelin and are indicated in green, 5HT3aR positive interneurons that express VIP are indicated in blue, chandelier and basket cells express PV and are indicated in purple, and finally, Martinotti cells that express SST are indicated in red. Both NGF cells and VIP+ interneurons are strongly responsive to nicotinergic and serotonergic neuromodulatory inputs and inputs from higher brain regions (feedback and callosal). NGF cells provide strong local inhibition through volume release of GABA mainly in the upper layers, but also in deeper layers. They inhibit all types of local excitatory and inhibitory neurons (not shown in figure). VIP interneurons mainly innervate other interneurons (SST+ and to a lesser extent PV+ interneurons). Basket cells are mainly innervated by thalamic (LGN) and local excitatory axons. They innervate the proximal dendrites and somata of pyramidal cells with a bias to layer 2/3 and layer 4. They receive inhibitory inputs from SST+ and VIP+ interneurons and other basket cells. Chandelier cells are special in the sense that they form inhibitory synapses on the axon initial segment of pyramidal cells (not shown in figure). Finally, Martinotti cells predominantly receive local inputs and preferentially form inhibitory synapses on distal dendrites and tufts of pyramidal cells

Fig. 3

Proposed model of plasticity substrate selection by different interneuron subsets during the critical period and in adulthood. When visual input is altered by monocular deprivation during the critical period, net inhibition provided by PV+ interneurons decreases, so that feedforward connections can undergo plastic changes (indicated by the red spot), which is sufficient for learning. In the adult visual system, perceptual learning is reinforcement dependent and may involve plasticity of feedback connections providing contextual information about the feedforward inputs that are reinforced (in this example, the black bar with the retinotopy and orientation matching the bird’s black wing). This plasticity is facilitated by reduced inhibition of SST+ interneurons that innervate the dendritic tufts. Suppression of SST+ interneuron activity is mediated through inhibition by VIP+ interneurons whose activity depends on the behavioral state of the animal