Cx3cr1-BAC-CRE-mediated knockout of toll-like receptor 4 alters mouse communicative behaviors, microglial morphology, and engulfment of synaptic material
Microglia, the tissue resident immune cells of the central nervous system, are critical regulators of postnatal neural circuit refinement. Innate immune receptors on microglia such as toll-like receptor 4 (TLR4) are best characterized in the context of inflammation, however, endogenous TLR4 ligands are generated during typical developmental processes. Here, we investigated whether TLR4 signaling…
Researchers have found that disabling a specific receptor in microglial cells, TLR4, affects the development of communication skills in mice. TLR4 is typically linked to inflammation response, but the study reveals its involvement in other crucial neural functions during typical development.
The study focused on CX3CR1-expressing myeloid cells, a subset of microglia, to understand how TLR4 signals influence microglial morphology, synaptic engulfment, and behavioral development in the absence of external stimuli. The researchers utilized a technique called TLR4 conditional knockout, which specifically targets this receptor in the aforementioned cells.
Interestingly, the mice lacking TLR4 in CX3CR1-expressing myeloid cells showed altered ultrasonic vocalizations during maternal separation, but no changes in social preference or anxiety-like behaviors. This suggests that TLR4 signaling in these specific cells plays a unique role in shaping neonatal communication.
Furthermore, the conditional knockout led to increased microglial ramification and cell volume within the paraventricular nucleus (PVN) of the hypothalamus. PVN is a brain region associated with hormonal regulation and cognitive functions. This alteration in microglial morphology could potentially impact the neural circuitry related to communication and related behaviors.
Another notable observation was a reduction in microglial engulfment of vGlut2-positive presynaptic material. Presynaptic material refers to the components of nerve cells that transmit signals, and engulfment is a process where microglia clear these materials. Despite this change, the overall number of excitatory synapses, which are connections between neurons that facilitate communication, remained unchanged.
This indicates that the microglia's role in synaptic maintenance is not disrupted by the absence of TLR4 signaling.
In conclusion, the study sheds light on the significant role of TLR4 signaling in CX3CR1-expressing microglial cells in shaping microglial morphology, presynaptic engulfment, and neonatal communicative behavior in mice. These findings suggest that TLR4 might be more involved in neural development and communication than previously thought, particularly in the context of microglial functions.
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