Both fornix and anterior thalamic, but not mammillary, lesions disrupt delayed non-matching-to-position memory in rats

doi:10.1016/S0166-4328(05)80020-8

Behavioural Brain Research

Volume 44, Issue 2, 29 August 1991, Pages 151-161

https://doi.org/10.1016/S0166-4328(05)80020-8 Get rights and content

Rats with radiofrequency lesions of the fimbria/fornix, or neurotoxic lesions of the mammillary bodies or the anterior thalamic nuclei weretested on their ability to perform a delayed non-matching-to-position task that had been learnt before surgery. In this task rats had to respond to a sample lever in an operant chamber and, after a variable delay (during which they were required to respond at the magazine tray), press the other lever when both were presented. Extensive mammillary body lesions had no effect on performance. In contrast, lesions in either the anterior thalamic nuclei or the fimbria/fornix produced marked deficits, the pattern of these deficits being consistent with a mnemonic impairment. It is argued that the anterior thalamic nuclei represent an important hippocampal output for spatial problems, but that the mammillary bodies are only necessary for certain types of mnemonic task.

References (37)

AggletonJ.P. et al.
The effects of mammilary body and combined amygdalar-fornix lesions on tests of delayed non-matching-to-sample in the rat
Behav. Brain Res.
(1990)
BeracocheaD.J. et al.
Effects of anterior or dorsomedial thalamic ibotenic lesions on learning and memory in rats
Behav. Neural Biol.
(1989)
BrierleyJ.B.
Neuropathology of amnesic states
CruceJ.A.F.
An autoradiographic study of the projections of the mammillothalamic tract in the rat
Brain Res.
(1975)
DunnettS.B. et al.
Cholinergic grafts in the neocortex or hippocampus of aged rats: reduction of delay-dependent deficits in the delayed non-matching to position task
Exp. Neurol.
(1988)
FieldT.D. et al.
Behavioral role of the mammillary efferent system
Brain Res. Bull.
(1978)
GreeneE. et al.
Thalamic role in spatial memory
Behav. Brain Res.
(1986)
HuntP.R. et al.
Medial dorsal thalamic lesions and working memory in the rats
Behav. Neural Biol.
(1991)
MeibachR.C. et al.
Thalamic projections of the hippocampal formation: evidence for an alternate pathway involving the internal capsule
Brain Res.
(1977)
RawlinsJ.N.P. et al.
The effects of fornix section on win-stay/lose-shift and win-shift/lose-stay performance in the rat
Behav. Brain Res.
(1988)

RawlinsJ.N.P. et al.

The septo-hippocampal system and cognitive mapping

RosenstockJ. et al.

The role of mammillary bodies in spatial memory

Exp. Neurol.

(1977)

SahgalA.

Vasopressing retards the acquisition of positively reinforced lever pressing in homozygous Brattleboro rats

Regul. Pept.

(1983)

SutherlandR.J. et al.

The role of the fornix/fimbria and some related subcortical structures in place learning and memory

Behav. Brain Res.

(1989)

AggletonJ.P. et al.

Memory impairments following restricted thalamic lesions in monkeys

Exp. Brain Res.

(1983)

AllenG.V. et al.

Mamillary body in the rat: topography and synaptology of projections from the subicular complex, prefrontal cortex, and midbrain tegmentum

J. Comp. Neurol.

(1989)

DunnettS.B.

Comparative effects of cholinergic drugs and lesions of nucleus basalis or fimbria-fornix on delayed matching in rats

Psychopharmacology

(1985)

DunnettS.B. et al.

Cholinergic blockade in prefrontal cortex and hippocampus disrupts shortterm memory in rats

NeuroReport

(1990)

Cited by (107)

Time to retire the serial Papez circuit: Implications for space, memory, and attention
2022, Neuroscience and Biobehavioral Reviews
After more than 80 years, Papez serial circuit remains a hugely influential concept, initially for emotion, but in more recent decades, for memory. Here, we show how this circuit is anatomically and mechanistically naïve as well as outdated. We argue that a new conceptualisation is necessitated by recent anatomical and functional findings that emphasize the more equal, working partnerships between the anterior thalamic nuclei and the hippocampal formation, along with their neocortical interactions in supporting, episodic memory. Furthermore, despite the importance of the anterior thalamic for mnemonic processing, there is growing evidence that these nuclei support multiple aspects of cognition, only some of which are directly associated with hippocampal function. By viewing the anterior thalamic nuclei as a multifunctional hub, a clearer picture emerges of extra-hippocampal regions supporting memory. The reformulation presented here underlines the need to retire Papez serially processing circuit.
Anterior thalamic dysfunction underlies cognitive deficits in a subset of neuropsychiatric disease models
2021, Neuron
Neuropsychiatric disorders are often accompanied by cognitive impairments/intellectual disability (ID). It is not clear whether there are converging mechanisms underlying these debilitating impairments. We found that many autism and schizophrenia risk genes are expressed in the anterodorsal subdivision (AD) of anterior thalamic nuclei, which has reciprocal connectivity with learning and memory structures. CRISPR-Cas9 knockdown of multiple risk genes selectively in AD thalamus led to memory deficits. While the AD is necessary for contextual memory encoding, the neighboring anteroventral subdivision (AV) regulates memory specificity. These distinct functions of AD and AV are mediated through their projections to retrosplenial cortex, using differential mechanisms. Furthermore, knockdown of autism and schizophrenia risk genes PTCHD1, YWHAG, or HERC1 from AD led to neuronal hyperexcitability, and normalization of hyperexcitability rescued memory deficits in these models. This study identifies converging cellular to circuit mechanisms underlying cognitive deficits in a subset of neuropsychiatric disease models.
The anterior thalamic nuclei and nucleus reuniens: So similar but so different
2020, Neuroscience and Biobehavioral Reviews
Citation Excerpt :
Inactivation of reuniens/rhomboid leads to severe deficits at delays as short of 1 s, indicative of a breakdown in task strategy that is not delay dependent (Hembrook et al., 2012). Meanwhile, anterior thalamic lesions cause delay-dependent deficits on a very similar automated nonmatching task (Aggleton et al., 1991). Given the severity of the spatial deficits, especially those after anterior thalamic damage, it is helpful to consider the selectivity of their effects.
Two thalamic sites are of especial significance for understanding hippocampal – diencephalic interactions: the anterior thalamic nuclei and nucleus reuniens. Both nuclei have dense, direct interconnections with the hippocampal formation, and both are directly connected with many of the same cortical and subcortical areas. These two thalamic sites also contain neurons responsive to spatial stimuli while lesions within these two same areas can disrupt spatial learning tasks that are hippocampal dependent. Despite these many similarities, closer analysis reveals important differences in the details of their connectivity and the behavioural impact of lesions in these two thalamic sites. These nuclei play qualitatively different roles that largely reflect the contrasting relative importance of their medial frontal cortex interactions (nucleus reuniens) compared with their retrosplenial, cingulate, and mammillary body interactions (anterior thalamic nuclei). While the anterior thalamic nuclei are critical for multiple aspects of hippocampal spatial encoding and performance, nucleus reuniens contributes, as required, to aid cognitive control and help select correct from competing memories.
Deep brain stimulation and cognition: Translational aspects
2020, Neurobiology of Learning and Memory
Many neurological patients suffer from memory loss. To date, pharmacological treatments for memory disorders have limited and short-lasting effects. Therefore, researchers are investigating novel therapies such as deep brain stimulation (DBS) to alleviate memory impairments. Up to now stimulation of the fornix, nucleus basalis of Meynert and entorhinal cortex have been found to enhance memory performance. Here, we provide an overview of the different DBS targets and mechanisms within the memory circuit, which could be relevant for enhancing memory in patients. Future studies are warranted, accelerating the efforts to further unravel mechanisms of action of DBS in memory-related disorders and develop stimulation protocols based on these mechanisms.
Early life stress leads to developmental and sex selective effects on performance in a novel object placement task
2017, Neurobiology of Stress
Disruptions in early life care, including neglect, extreme poverty, and trauma, influence neural development and increase the risk for and severity of pathology. Significant sex disparities have been identified for affective pathology, with females having an increased risk of developing anxiety and depressive disorder. However, the effects of early life stress (ELS) on cognitive development have not been as well characterized, especially in reference to sex specific impacts of ELS on cognitive abilities over development. In mice, fragmented maternal care resulting from maternal bedding restriction, was used to induce ELS. The development of spatial abilities were tracked using a novel object placement (NOP) task at several different ages across early development (P21, P28, P38, P50, and P75). Male mice exposed to ELS showed significant impairments in the NOP task compared with control reared mice at all ages tested. In female mice, ELS led to impaired NOP performance immediately following weaning (P21) and during peri-adolescence (P38), but these effects did not persist into early adulthood. Prior work has implicated impaired hippocampus neurogenesis as a possible mediator of negative outcomes in ELS males. In the hippocampus of behaviorally naïve animals there was a significant decrease in expression of Ki-67 (proliferative marker) and doublecortin (DCX-immature cell marker) as mice aged, and a more rapid developmental decline in these markers in ELS reared mice. However, the effect of ELS dissipated by P28 and no main effect of sex were observed. Together these results indicate that ELS impacts the development of spatial abilities in both male and female mice and that these effects are more profound and lasting in males.
The effect of pharmacological inactivation of the mammillary body and anterior thalamic nuclei on hippocampal theta rhythm in urethane-anesthetized rats
2017, Neuroscience
Citation Excerpt :
These findings clearly show that the anterior thalamus may influence hippocampal activity and our results indicate that it may also concern theta rhythm activity. Lesions of the anterior thalamus usually produce equivalent or more severe memory deficits than lesions of the mammillary body (e.g. Sutherland and Rodriguez, 1989; Aggleton et al., 1991, 1995; Gaffan et al., 2001 for more details see Vann, 2010), however it needs to be stressed that all these studies have concerned lesions of the whole structures, the ATN and MB. In conclusion, our study revealed for the first time that inactivation of the MM and AV leads to disruption of theta rhythm activity in the structures of the extended hippocampal system.
The mammillary body (MB) and the anterior thalamic nuclei (ATN) are closely related structures, which take part in learning and memory processes. However, the exact role of these structures has remained unclear. In both structures neurons firing according to hippocampal theta rhythm have been found, mainly in the medial mammillary nucleus (MM) and anteroventral thalamic nucleus (AV). These neurons are driven by descending projections from the hippocampal formation and are thought to convey theta rhythm back to the hippocampus (HP). We argue that the MB–ATN axis not only relays theta signal, but may also modulate it. To examine it, we performed a pharmacological inactivation of the MM and AV by local infusion of procaine, and measured changes in theta activity in selected structures of the extended hippocampal system in urethane-anesthetized rats. The inactivation of the MM resulted in decrease in EEG power in the HP and AV, the most evidently in the lower theta frequency bands, i.e. 3–5 Hz in the HP (down to 9.2% in 3- to 4-Hz band and 37.6% in 4- to 5-Hz band, in comparison to the power in the control conditions) and 3–4 Hz in the AV (down to 24.9%). After the AV inactivation, hippocampal EEG power decreased in theta frequency bands of 3–8 Hz (down to 61.6% in 6- to 7-Hz band and 69.4% in 7- to 8-Hz band). Our results suggest that the role of the MB–ATN axis in regulating theta rhythm signaling may be much more important than has been speculated so far.

View all citing articles on Scopus

View full text

Both fornix and anterior thalamic, but not mammillary, lesions disrupt delayed non-matching-to-position memory in rats

Behav. Brain Res.

Behav. Neural Biol.

Brain Res.

Exp. Neurol.

Brain Res. Bull.

Behav. Brain Res.

Behav. Neural Biol.

Brain Res.

Behav. Brain Res.

Exp. Neurol.

Regul. Pept.

Behav. Brain Res.

Memory impairments following restricted thalamic lesions in monkeys

Exp. Brain Res.

Mamillary body in the rat: topography and synaptology of projections from the subicular complex, prefrontal cortex, and midbrain tegmentum

J. Comp. Neurol.

Comparative effects of cholinergic drugs and lesions of nucleus basalis or fimbria-fornix on delayed matching in rats

Psychopharmacology

Cholinergic blockade in prefrontal cortex and hippocampus disrupts shortterm memory in rats

NeuroReport