The effect of pharmacological inactivation of the mammillary body and anterior thalamic nuclei on hippocampal theta rhythm in urethane-anesthetized rats
“…This is important given the influence of the supramammillary nuclei on hippocampal theta frequency (e.g., Kirk, 1998). As such, previous studies that have assessed the effects of MB lesions, or inactivation, on hippocampal theta can be difficult to interpret when damage extends into the overlying supramammillary nuclei (Sharp and Koester, 2008; Zakowski et al, 2017), and vice versa (Renouard et al, 2015). Nevertheless, the only previous study that has examined hippocampal theta following MB manipulation in nonanesthetized animals established a similar pattern of changes to those reported here, with a reduction in hippocampal theta frequency (Sharp and Koester, 2008).…”
Diencephalic amnesia can be as debilitating as the more commonly known temporal lobe amnesia, yet the precise contribution of diencephalic structures to memory processes remains elusive. Across four cohorts of male rats, we used discrete lesions of the mammillothalamic tract to model aspects of diencephalic amnesia and assessed the impact of these lesions on multiple measures of activity and plasticity within the hippocampus and retrosplenial cortex. Lesions of the mammillothalamic tract had widespread indirect effects on hippocampocortical oscillatory activity within both theta and gamma bands. Both within-region oscillatory activity and cross-regional synchrony were altered. The network changes were state-dependent, displaying different profiles during locomotion and paradoxical sleep. Consistent with the associations between oscillatory activity and plasticity, complementary analyses using several convergent approaches revealed microstructural changes, which appeared to reflect a suppression of learning-induced plasticity in lesioned animals. Together, these combined findings suggest a mechanism by which damage to the medial diencephalon can impact upon learning and memory processes, highlighting an important role for the mammillary bodies in the coordination of hippocampocortical activity.
SIGNIFICANCE STATEMENT
Information flow within the Papez circuit is critical to memory. Damage to ascending mammillothalamic projections has consistently been linked to amnesia in humans and spatial memory deficits in animal models. Here we report on the changes in hippocampocortical oscillatory dynamics that result from chronic lesions of the mammillothalamic tract and demonstrate, for the first time, that the mammillary bodies, independently of the supramammillary region, contribute to frequency modulation of hippocampocortical theta oscillations. Consistent with the associations between oscillatory activity and plasticity, the lesions also result in a suppression of learning-induced plasticity. Together, these data support new functional models whereby mammillary bodies are important for coordinating hippocampocortical activity rather than simply being a relay of hippocampal information as previously assumed.
“…This is important given the influence of the supramammillary nuclei on hippocampal theta frequency (e.g., Kirk, 1998). As such, previous studies that have assessed the effects of MB lesions, or inactivation, on hippocampal theta can be difficult to interpret when damage extends into the overlying supramammillary nuclei (Sharp and Koester, 2008; Zakowski et al, 2017), and vice versa (Renouard et al, 2015). Nevertheless, the only previous study that has examined hippocampal theta following MB manipulation in nonanesthetized animals established a similar pattern of changes to those reported here, with a reduction in hippocampal theta frequency (Sharp and Koester, 2008).…”
Diencephalic amnesia can be as debilitating as the more commonly known temporal lobe amnesia, yet the precise contribution of diencephalic structures to memory processes remains elusive. Across four cohorts of male rats, we used discrete lesions of the mammillothalamic tract to model aspects of diencephalic amnesia and assessed the impact of these lesions on multiple measures of activity and plasticity within the hippocampus and retrosplenial cortex. Lesions of the mammillothalamic tract had widespread indirect effects on hippocampocortical oscillatory activity within both theta and gamma bands. Both within-region oscillatory activity and cross-regional synchrony were altered. The network changes were state-dependent, displaying different profiles during locomotion and paradoxical sleep. Consistent with the associations between oscillatory activity and plasticity, complementary analyses using several convergent approaches revealed microstructural changes, which appeared to reflect a suppression of learning-induced plasticity in lesioned animals. Together, these combined findings suggest a mechanism by which damage to the medial diencephalon can impact upon learning and memory processes, highlighting an important role for the mammillary bodies in the coordination of hippocampocortical activity.
SIGNIFICANCE STATEMENT
Information flow within the Papez circuit is critical to memory. Damage to ascending mammillothalamic projections has consistently been linked to amnesia in humans and spatial memory deficits in animal models. Here we report on the changes in hippocampocortical oscillatory dynamics that result from chronic lesions of the mammillothalamic tract and demonstrate, for the first time, that the mammillary bodies, independently of the supramammillary region, contribute to frequency modulation of hippocampocortical theta oscillations. Consistent with the associations between oscillatory activity and plasticity, the lesions also result in a suppression of learning-induced plasticity. Together, these data support new functional models whereby mammillary bodies are important for coordinating hippocampocortical activity rather than simply being a relay of hippocampal information as previously assumed.
“…This is important given the influence of the supramammillary nuclei on hippocampal theta frequency (e.g., Kirk, 1998). As such, many studies that have assessed the effects of mammillary body lesions, or inactivation, on hippocampal theta can be difficult to interpret when damage extends into the overlying supramammillary nuclei (Sharp and Koester, 2008;Zakowski et al, 2017) and vice versa (Renouard et al, 2015). Nevertheless, the only previous study that has examined hippocampal theta following mammillary body manipulation in non-anesthetized animals established a similar pattern of changes to those reported here, with a reduction in hippocampal theta-frequency (Sharp and Koester, 2008).…”
for technical, histological and surgical assistance.
AbstractDiencephalic amnesia can be as disruptive as the more commonly known temporal lobe amnesia, yet the precise contribution of diencephalic structures to memory processes remains elusive. We used discrete lesions of the mammillothalamic tract to model aspects of diencephalic amnesia and assessed the impact of these lesions on multiple measures of activity and plasticity within the hippocampus and retrosplenial cortex. Lesions of the mammillothalamic tract had widespread indirect effects on hippocampo-cortical oscillatory activity within both theta and gamma bands. Both within-region oscillatory activity and cross-regional synchrony were altered. The network changes were state-dependent, displaying different profiles during locomotion and paradoxical sleep. Consistent with the associations between oscillatory activity and plasticity, complementary analyses using several convergent approaches revealed microstructural changes, which appeared to reflect a suppression of learning-induced plasticity in lesioned animals. Together, these combined findings suggest a mechanism by which damage to the medial diencephalon can impact upon learning and memory processes, highlighting important role for the mammillary bodies in the co-ordination of hippocampo-cortical activity.
“…Importantly, however, while it is known that the AD head direction signal is driven by lateral MB, it is not yet clear to what extent AV/AM theta-related directional activity is dependent on mammillothalamic inputs. ATN theta, however, is at least partly driven by the MBs, as procaine infusions into the MBs of anaesthetised rats reduces AV theta power ( Zakowski et al, 2017 ). Furthermore, theta activity in AV is unaffected by dorsal hippocampal lesions, again suggesting that, similar to the supramammillary nucleus ( Kirk and McNaughton, 1991 ), the MB-ATN pathway forms a medial diencephalic theta network that arises independently of the hippocampus ( Talk et al, 2004 ).…”
“…Furthermore, inactivation of the ATN impairs grid cell periodicity in the entorhinal cortex ( Winter et al, 2015 ). Under anaesthesia, both MB and ATN inactivation attenuate hippocampal theta and MB inactivation reduces theta power in AV ( Zakowski et al, 2017 ), highlighting the importance on ascending MB projections for theta-related firing across memory networks. Fig.…”
Section: How Might the Mammillothalamic Pathway Contribute To Contextual Encoding?mentioning
Highlights
The mammillothalamic pathway plays a key role in temporal and contextual memory.
The mammillothalamic pathway mediates hippocampo-cortical functions.
The mammillothalamic pathway plays an important role in oscillatory co- ordination.
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