Theta-rhythmically firing neurons in the anterior thalamus: implications for mnemonic functions of Papez's circuit. Academic Article uri icon


  • In 1937 Papez described an anatomical circuit (or loop) beginning and ending in the hippocampal formation that he proposed subserved emotional experience (Papez, 1937). Specifically, the projections of the circuit were as follows: hippocampal formation--> mammillary bodies--> anterior thalamus--> cingulate cortex--> parahippocampal gyrus--> hippocampal formation. Although the circuit has been refined based on subsequent anatomical findings (Amaral and Witter, 1995; Shibata, 1992; Van Groen and Wyss, 1995), the major links of the circuit unquestionably represent a prominent system of connections in the mammalian brain. Hence, the enduring nature of 'Papez's circuit'. Unlike, however, its persistence as anatomical entity, the proposed functional role for the circuit has been less resilient. The early notion that Papez's circuit subserves emotional experience/expression has been abandoned (LeDoux, 1993) and replaced by the proposal that it is primarily involved in mnemonic functions (Aggleton and Brown, 1999). Lesions of each of the major components of the circuit have been shown to disrupt memory (Aggleton and Brown, 1999; Sutherland et al., 1988; Sziklas and Petrides, 1993). The mammillary bodies represent a major output from the hippocampus in Papez's circuit (Amaral and Witter, 1995). It has recently been shown that cells of mammillary body fire rhythmically in bursts synchronous with the theta rhythm of the hippocampus (Bland et al., 1995; Kirk et al., 1996; Kocsis and Vertes, 1994, 1997) and that this rhythmical activity is dependent upon the action of the hippocampus on the mammillary bodies (Bland et al., 1995; Kirk et al., 1996). It is well established that the mammillary bodies project massively to the anterior thalamus (Shibata, 1992), which taken together with the demonstration that mammillary body cells fire synchronously with theta, suggests that the mammillary bodies may act on the anterior thalamus, possibly in the manner that the hippocampus acts on the mammillary bodies, to rhythmically activate cells of the anterior thalamus at theta frequency. We demonstrated that approximately 75% of cells of the anterior ventral nucleus of the thalamus fire rhythmically synchronous with the hippocampal theta rhythm and the activity of 46% of these anterior ventral neurons was highly correlated with theta. These findings, together with demonstration of theta-rhythmically firing cells in other structures of Papez's circuit, indicate that a theta-rhythmic signal may resonate throughout Papez's circuit, possibly involved in the control of mnemonic functions of the circuit.

publication date

  • 2001