Lesions to the CA2 region of the hippocampus impair social memory in mice

Abstract

The function of the CA2 region of the hippocampus is poorly understood. While the CA1 and CA3 regions have been extensively studied, for years the CA2 region has primarily been viewed as a linking area between the two. However, the CA2 region is known to have distinct neurochemical and structural features that are different from the other parts of hippocampus and in recent years it has been suggested that the CA2 region may play a role in the formation and or recall of olfactory-based memories needed for normal social behavior. While this hypothesis has been supported by hippocampal lesion studies that have included the CA2 region, no studies have attempted to specifically lesion the CA2 region of the hippocampus in mice to determine the effects on social recognition memory and olfaction. To fill this knowledge gap, we sought to perform excitotoxic N-methyl-D aspartate (NMDA) lesions of the CA2 region in mice and determine the effects on social recognition memory. We predicted that lesions of the CA2 region would impair social recognition memory. We then went on to test olfaction in CA2 lesioned mice since social memory requires a functional olfactory system. Consistent with our prediction, we found that CA2 lesioned animals have impaired social recognition. These findings are significant because they confirm that the CA2 region of the hippocampus is a part of the neural circuitry that regulates social recognition memory, which may have implications for our understanding of the neural regulation of social behavior across species.

The olfactory bulbectomized rat as a model of depression: The hippocampal pathway

“…The DG, CA1, CA2 and CA3 regions are important to depression, as adult neurogenesis occurs in the DG and antidepressants increases neurogenesis [59] and the CA2 is important for normal social memory [58,60]. Moreover, in the next sections we will discuss alterations in CA1 and CA3 regions.…”

Voltage imaging to understand connections and functions of neuronal circuits

“…Furthermore, longterm depression of the excitation of CA2 inhibitory interneurons permitted distal excitation of CA2 pyramidal neurons, allowing them to fire and relay activity to CA1 (Nasrallah et al 2015). The significance of CA2 and its connections was recently highlighted as critical for social memory (Hitti and Siegelbaum 2014;Stevenson and Caldwell 2014) and in a mouse model of schizophrenia where CA2 is functionally disconnected from the trisynaptic pathway by excessive feedforward inhibition (Piskorowski et al 2016).…”

Hippocampal CA2 Region: A New Player in Social Dysfunctions

“…Several interventional studies have shed some light on this question. Knockout of vasopressin 1b receptor (V1bR) in mouse CA2 resulted in impairment in tasks that require remembering the temporal order of presented objects [41]. Recently, in vivo recording in behaving rats demonstrates that individual CA2 cells display standard firing patterns as in CA1 and CA3.…”

“…Vasopressin 1b receptor (V1bR), one principal receptor mediating social aggression in rodents, was found prominent expression within the CA2 pyramidal cells but much lower expression in the hypothalamic paraventricular nucleus and amygdala [41]. Knockout of vasopressin 1b receptor in mouse CA2 reduces aggression and impairs social recognition, but spares spatial learning [42].…”