Gap junctions in developing thalamic and neocortical neuronal networks

Abstract

The presence of direct, cytoplasmatic, communication between neurons in the brain of vertebrates has been demonstrated a long time ago. These gap junctions have been characterized in many brain areas in terms of subunit composition, biophysical properties, neuronal connectivity patterns, and developmental regulation. Although interesting findings emerged, showing that different subunits are specifically regulated during development, or that excitatory and inhibitory neuronal networks exhibit various electrical connectivity patterns, gap junctions did not receive much further interest. Originally, it was believed that gap junctions represent simple passageways for electrical and biochemical coordination early in development. Today, we know that gap junction connectivity is tightly regulated, following independent developmental patterns for excitatory and inhibitory networks. Electrical connections are important for many specific functions of neurons, and are, for example, required for the development of neuronal stimulus tuning in the visual system. Here, we integrate the available data on neuronal connectivity and gap junction properties, as well as the most recent findings concerning the functional implications of electrical connections in the developing thalamus and neocortex.

Keywords: connexin; electrical synapse; gap junctions; neocortex; thalamus.

Figure 1.

Electrical connectivity changes for cortical and thalamic neurons during development. (A) Cortical pyramidal neurons exhibit their highest connectivity rate during the first postnatal week; during the next 2 postnatal weeks, connectivity rates decrease considerably, and become almost absent in adult animals. (B) Cortical fast-spiking (FS) cells are possibly less interconnected during the first postnatal week than during the third postnatal week. Neurons of different classes, like low-threshold spiking (LTS) and pyramidal cell (PC), connect to FS cells at much lower rates than other FS cells, during the third week; PCs and LTS neurons possibly connect to FS cells at a similar or higher rate immediately after birth. Upon reaching adulthood, FS cells may lose all connections to neurons of different classes while maintaining high electrical connectivity with each other. (C) The inhibitory neurons of the TRN (thalamic reticular nucleus) have a high connectivity rate during the first postnatal week when compared with the excitatory neurons of ventrobasal nucleus (VBN). During the next 2 postnatal weeks, TRN neuron electrical connectivity rate remains the same while the junctional conductance increases; VBN neurons become less electrically connected. In adults, gap junctions appear to be still extensively present within the TRN whereas in the VBN they are absent. Each line connecting 2 cells is equivalent to 5%–10% of connectivity rate; see Table 1 for details. A: Peinado et al. 1993; Wang et al. 2010; Yu et al. 2012; B: Gibson et al. 1999; Meyer et al. 2002; Pangratz-Fuehrer and Hestrin 2011; C: Fuentealba et al. 2004; Parker et al. 2009; Lee et al. 2010.

Figure 2.

Plasticity of coupling strength as a consequence of development and electrical activity. (A) From the first postnatal week (Aa) to the second (Ab), there is an 8-fold increase in g_j (junctional conductance), possibly as a consequence of a decrease in the R_i (input resistance) of a similar magnitude (Parker et al. 2009). (B) After 2 TRN neurons are simultaneously active for a number of times (Ba, upper cell pair), the electrical connection between them decreases in strength, symmetrically (Bb, upper cell pair); when only one cell in the pair is active (Ba, lower cell pair), the electrical connection also decreases in strength, but in an asymmetric way, the formerly active cell being able to receive less input than it can send to the other cell (Bb, lower cell pair; Haas et al. 2011).

Figure 3.

Gap junction presence during the first postnatal week influences orientation selectivity tuning. (A) In the visual cortex of the mouse, during the first postnatal week, clonally related neurons are 10 times more likely to connect to each other than to an unrelated neuron; connections between sister cells have a junctional conductance 3-fold higher than other connections (Aa) (Yu et al. 2012); if electrical connectivity is maintained, around P12–17, clonally related cells develop identical orientation preferences (Ab; Li et al. 2012). If gap junctions are blocked during the first postnatal week (Ba), the sister cells develop separately, exhibiting different orientation selectivity preferences (Bb).