Functional mapping of reward responses in the lateral septum along the dorsoventral axis Restricted; Files Only
Karkare, Sonia (Spring 2023)
Abstract
The lateral septum (LS) has been implicated in a wide range of behaviors, including aggression, reward-related behaviors, kin recognition, sexual behaviors, and social memory. While the specific role of the LS in mediating such a variety of behaviors is unclear, its anatomical heterogeneity has been suggested as a putative contributor to its functional diversity. Discrete LS compartments have been identified by specific properties, such as connectivity with the hippocampus and hypothalamus, as well as the differential expression of receptors and neuropeptides. Recent evidence suggests that subregions of the LS might play a role in modulating both approach and avoidance behaviors. In particular, there appears to be functional clustering of neurons along the dorsoventral (DV) axis within the LS, with approach behaviors modulated by neurons localized to the dorsal subdivision of the LS, while avoidance behaviors are mediated by neurons in the ventral LS. However, it is unclear how reward responses are organized along the DV axis of the LS. In this study, we performed monosynaptic rabies tracing experiments to characterize the patterns of inputs to different LS projection populations. Additionally, we performed cellular resolution calcium imaging in different positions along the DV axis of the LS during an operant reward task to determine how reward responses are organized along the DV axis of the LS. We did not find significant differences in proportions of input neurons to the projection populations in our tracing experiments suggesting that different LS projection populations receive similar patterns of inputs across various brain regions. We found interesting differences in the reward-related activity along the DV axis in the pilot cohort of animals suggesting that dorsal and ventral populations of LS likely play different roles in reward-related behaviors. Future studies will be required to validate this result, as well as to further ascertain the identities of the imaged neurons and the causal role they play in mediating behavior.
Table of Contents
Table of Contents
Introduction……………………………………………………………………………………
1
Anatomy of the LS……………………………………………………………………………...
2
Figure 1: Divisions of the LS…………………………………………………………...
2
LS connectivity…………………………………………………………………………
3
mRNA distribution……………………………………………………………………..
3
DV organization of the LS……………………………………………………………………...
5
Approach, avoidance, and aggression………………………………………………….
5
Reward………………………………………………………………………………….
6
Aims and results………………………………………………………………………………..
7
Results………………………………………………………………………………………….
8
LS projection populations receive largely overlapping brain-wide inputs……………………..
8
Figure 2: Monosynaptic rabies tracing…………………………………………………
9
Figure 3: Wholebrain software analysis………………………………………………..
9
Figure 4: Anatomical locations of subcortical downstream targets of the LS………….
10
Figure 5: Distributions of monosynaptic inputs to LS projection populations…………
12
Figure 6: Quantification of monosynaptic inputs to LS projection populations……….
13
Starter cell populations occupy distinct compartments of the LS……………………………...
14
Figure 7: Representative starter cell locations along the DV axis of the LS…………...
14
Both excitatory and inhibitory reward-responsive neurons are found along the LS DV axis….
15
Figure 8: Cellular resolution calcium imaging…………………………………………
15
Figure 9: Behavioral paradigm and example results…………………………………...
17
Figure 10: Time-locked excitatory and inhibitory reward-responses of LS neurons along the DV axis………………………………………………………………………………
.
18
Excitatory reward-responsive neurons show varying temporal dynamics in the dorsal and ventral LS……………………………………………………………………………………….
.
19
Figure 11: Temporal dynamics of excitatory reward responses in LSd, LSi, and LSv...
20
Activity of LS neurons differs on rewarded and unrewarded trials…………………………….
22
Figure 12: Decoding of neural activity on rewarded and unrewarded trials…………...
22
Discussion……………………………………………………………………………………...
24
Anatomically positioned as a functional hub rather than relay station…………………………
24
Temporal dynamics of LS reward responses along the DV axis……………………………….
25
Lateral inhibition……………………………………………………………………………….
26
Limitations and future directions………………………………………………………………
27
Figure 12: Tracking neurons across training…………………………………………...
28
Methods………………………………………………………………………………………...
29
References……………………………………………………………………………………...
36
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File download under embargo until 19 May 2025 | 2023-04-05 16:15:01 -0400 | File download under embargo until 19 May 2025 |
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