Hippocampus and Entorhinal Cortex Recruit Cholinergic and NMDA Receptors Separately to Generate Hippocampal Theta Oscillations

AbstractThe supramammillary region (SuM) is a posterior hypothalamic structure, known to regulate hippocampal theta oscillations and arousal. However, recent studies reported that the stimulation of SuM neurons with neuroactive chemicals, including substances of abuse, is reinforcing. We conducted experiments to elucidate how SuM neurons mediate such effects. Using optogenetics, we found that the excitation of SuM glutamatergic (GLU) neurons was reinforcing in mice; this effect was relayed by their projections to septal GLU neurons. SuM neurons were active during exploration and approach behavior and diminished activity during sucrose consumption. Consistently, inhibition of SuM neurons disrupted approach responses, but not sucrose consumption. Such functions are similar to those of mesolimbic dopamine neurons. Indeed, the stimulation of SuM-to-septum GLU neurons and septum-to-ventral tegmental area (VTA) GLU neurons activated mesolimbic dopamine neurons. We propose that the supramammillo-septo-VTA pathway regulates arousal that reinforces and energizes behavioral interaction with the environment.

Conceptualization and validation of an open-source closed-loop deep brain stimulation system in rat

Scientific Reports ◽

10.1038/srep09921 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 15

Author(s):

Hemmings Wu ◽

Hartwin Ghekiere ◽

Dorien Beeckmans ◽

Tim Tambuyzer ◽

Kris van Kuyck ◽

...

Keyword(s):

Electrical Stimulation ◽

Deep Brain Stimulation ◽

Open Source ◽

Brain Stimulation ◽

Closed Loop ◽

Symptom Control ◽

Theta Oscillations ◽

Open Source Hardware ◽

Hippocampal Theta ◽

Deep Brain

Abstract Conventional deep brain stimulation (DBS) applies constant electrical stimulation to specific brain regions to treat neurological disorders. Closed-loop DBS with real-time feedback is gaining attention in recent years, after proved more effective than conventional DBS in terms of pathological symptom control clinically. Here we demonstrate the conceptualization and validation of a closed-loop DBS system using open-source hardware. We used hippocampal theta oscillations as system input and electrical stimulation in the mesencephalic reticular formation (mRt) as controller output. It is well documented that hippocampal theta oscillations are highly related to locomotion, while electrical stimulation in the mRt induces freezing. We used an Arduino open-source microcontroller between input and output sources. This allowed us to use hippocampal local field potentials (LFPs) to steer electrical stimulation in the mRt. Our results showed that closed-loop DBS significantly suppressed locomotion compared to no stimulation and required on average only 56% of the stimulation used in open-loop DBS to reach similar effects. The main advantages of open-source hardware include wide selection and availability, high customizability and affordability. Our open-source closed-loop DBS system is effective and warrants further research using open-source hardware for closed-loop neuromodulation.

Flexible theta sequence compression mediated via phase precessing interneurons

eLife ◽

10.7554/elife.20349 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 8

Author(s):

Angus Chadwick ◽

Mark CW van Rossum ◽

Matthew F Nolan

Keyword(s):

Action Potentials ◽

High Capacity ◽

Theta Oscillations ◽

Sequence Generation ◽

Spike Sequences ◽

Theta Frequency ◽

Neural Substrate ◽

Hippocampal Theta ◽

Novel Model ◽

Sequence Compression

Encoding of behavioral episodes as spike sequences during hippocampal theta oscillations provides a neural substrate for computations on events extended across time and space. However, the mechanisms underlying the numerous and diverse experimentally observed properties of theta sequences remain poorly understood. Here we account for theta sequences using a novel model constrained by the septo-hippocampal circuitry. We show that when spontaneously active interneurons integrate spatial signals and theta frequency pacemaker inputs, they generate phase precessing action potentials that can coordinate theta sequences in place cell populations. We reveal novel constraints on sequence generation, predict cellular properties and neural dynamics that characterize sequence compression, identify circuit organization principles for high capacity sequential representation, and show that theta sequences can be used as substrates for association of conditioned stimuli with recent and upcoming events. Our results suggest mechanisms for flexible sequence compression that are suited to associative learning across an animal’s lifespan.

Optogenetic activation of SST-positive interneurons restores hippocampal theta oscillation impairment induced by soluble amyloid beta oligomersin vivo

10.1101/465112 ◽

2018 ◽

Author(s):

Hyowon Chung ◽

Kyerl Park ◽

Hyun Jae Jang ◽

Michael M Kohl ◽

Jeehyun Kwag

Keyword(s):

Learning And Memory ◽

Peak Power ◽

Pyramidal Neurons ◽

Hippocampal Slices ◽

Field Potential ◽

Theta Oscillations ◽

Ca1 Pyramidal Neurons ◽

Theta Frequency ◽

Hippocampal Theta

AbstractAbnormal accumulation of amyloid β oligomers (AβO) is a hallmark of Alzheimer’s disease (AD), which leads to learning and memory deficits. Hippocampal theta oscillations that are critical in spatial navigation, learning and memory are impaired in AD. Since GABAergic interneurons, such as somatostatin-positive (SST+) and parvalbumin-positive (PV+) interneurons, are believed to play key roles in the hippocampal oscillogenesis, we asked whether AβO selectively impairs these SST+ and PV+ interneurons. To selectively manipulate SST+ or PV+ interneuron activity in mice with AβO pathologyin vivo, we co-injected AβO and adeno-associated virus (AAV) for expressing floxed channelrhodopsin-2 (ChR2) into the hippocampus of SST-Cre or PV-Cre mice. Local field potential (LFP) recordingsin vivoin these AβO–injected mice showed a reduction in the peak power of theta oscillations and desynchronization of spikes from CA1 pyramidal neurons relative to theta oscillations compared to those in control mice. Optogenetic-activation of SST+ but not PV+ interneurons in AβO–injected mice fully restored the peak power of theta oscillations and resynchronized the theta spike phases to a level observed in control mice.In vitrowhole-cell voltage-clamp recordings in CA1 pyramidal neurons in hippocampal slices treated with AβO revealed that short-term plasticity of SST+ interneuron inhibitory inputs to CA1 pyramidal neurons at theta frequency were selectively disrupted while that of PV+ interneuron inputs were unaffected. Together, our results suggest that dysfunction in inputs from SST+ interneurons to CA1 pyramidal neurons may underlie the impairment of theta oscillations observed in AβO-injected micein vivo.Our findings identify SST+ interneurons as a target for restoring theta-frequency oscillations in early AD.

A Neural Model of Intrinsic and Extrinsic Hippocampal Theta Rhythms: Anatomy, Neurophysiology, and Function

Frontiers in Systems Neuroscience ◽

10.3389/fnsys.2021.665052 ◽

2021 ◽

Vol 15 ◽

Author(s):

Stephen Grossberg

Keyword(s):

Entorhinal Cortex ◽

Category Learning ◽

Neural Model ◽

Brain Regions ◽

Beta Oscillations ◽

Emotional Processes ◽

Theoretical Synthesis ◽

Multiple Species ◽

And Function ◽

Hippocampal Theta

This article describes a neural model of the anatomy, neurophysiology, and functions of intrinsic and extrinsic theta rhythms in the brains of multiple species. Topics include how theta rhythms were discovered; how theta rhythms organize brain information processing into temporal series of spatial patterns; how distinct theta rhythms occur within area CA1 of the hippocampus and between the septum and area CA3 of the hippocampus; what functions theta rhythms carry out in different brain regions, notably CA1-supported functions like learning, recognition, and memory that involve visual, cognitive, and emotional processes; how spatial navigation, adaptively timed learning, and category learning interact with hippocampal theta rhythms; how parallel cortical streams through the lateral entorhinal cortex (LEC) and the medial entorhinal cortex (MEC) represent the end-points of the What cortical stream for perception and cognition and the Where cortical stream for spatial representation and action; how the neuromodulator acetylcholine interacts with the septo-hippocampal theta rhythm and modulates category learning; what functions are carried out by other brain rhythms, such as gamma and beta oscillations; and how gamma and beta oscillations interact with theta rhythms. Multiple experimental facts about theta rhythms are unified and functionally explained by this theoretical synthesis.

Alternating sequences of future and past behavior encoded within hippocampal theta oscillations

Science ◽

10.1126/science.abb4151 ◽

2020 ◽

Vol 370 (6513) ◽

pp. 247-250 ◽

Cited By ~ 3

Author(s):

Mengni Wang ◽

David J. Foster ◽

Brad E. Pfeiffer

Keyword(s):

Activity Patterns ◽

Place Cells ◽

Theta Oscillations ◽

Retrospective Evaluation ◽

Past Behavior ◽

Hippocampal Ca1 ◽

Ongoing Behavior ◽

Theta Phase ◽

Hippocampal Theta ◽

And Storage

Neural networks display the ability to transform forward-ordered activity patterns into reverse-ordered, retrospective sequences. The mechanisms underlying this transformation remain unknown. We discovered that, during active navigation, rat hippocampal CA1 place cell ensembles are inherently organized to produce independent forward- and reverse-ordered sequences within individual theta oscillations. This finding may provide a circuit-level basis for retrospective evaluation and storage during ongoing behavior. Theta phase procession arose in a minority of place cells, many of which displayed two preferred firing phases in theta oscillations and preferentially participated in reverse replay during subsequent rest. These findings reveal an unexpected aspect of theta-based hippocampal encoding and provide a biological mechanism to support the expression of reverse-ordered sequences.