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Breathing and heartbeat synchronize to each other and to brain function and affect cognition in humans. However, it is not clear how cardiorespiratory rhythms modulate such basic processes as synaptic plasticity thought to underlie learning. Thus, we studied if respiration and cardiac cycle phases at burst stimulation onset affect hippocampal long-term potentiation (LTP) in the CA3–CA1 synapse in urethane-anesthetized adult male Sprague–Dawley rats. In a between-subjects design, we timed burst stimulation of the ventral hippocampal commissure (vHC) to systole or diastole either during expiration or inspiration and recorded responses throughout the hippocampus with a linear probe. As classical conditioning in humans seems to be most efficient at expiration-diastole, we also expected LTP to be most efficient if burst stimulation was targeted to expiration-diastole. However, LTP was induced equally in all four groups and respiration and cardiac cycle phase did not modulate CA1 responses to vHC stimulation overall. This could be perhaps because we bypassed all natural routes of external influences on the CA1 by directly stimulating the vHC. In the future, the effect of cardiorespiratory rhythms on synaptic plasticity could also be studied in awake state and in other parts of the hippocampal tri-synaptic loop. peerReviewed

Dentate gyrus (DG) is important for pattern separation and spatial memory, and it is thought to gate information flow to the downstream hippocampal subregions. Dentate spikes (DSs) are high-amplitude, fast, positive local-field potential events taking place in the DG during immobility and sleep, and they have been connected to memory consolidation in rodents. DSs are a result of signaling from the entorhinal cortex (EC) to the DG, and they suppress firing of pyramidal cells in the CA3 and CA1. To study the effects of DSs to signaling in the hippocampal tri-synaptic loop, we electrically stimulated the afferent fibers of the DG, CA3, and CA1 in adult male Sprague–Dawley rats at different delays from DSs. Responses to stimulation were increased in the EC-DG synapse during DSs, and the effect was amplified after theta-burst stimulation. We concluded that DSs strengthen the excitatory signal from the EC to the DG, which is reinforced by synapse potentiation and increased excitability of granule cells after theta-burst stimulation. This signal boosting may function in enhancing plastic changes in the DG-CA3 synapse. As responses in the CA3 and CA1 remained unaffected by the DS, the DS-contingent silencing of pyramidal cells seems to be a result of a decrease in excitatory input rather than a decrease in the excitability of the pyramidal cells themselves. In addition, we found that the DSs occur asynchronously in the left and right hippocampi, giving novel evidence of lateralization of the rodent hippocampus. peerReviewed

Rhythms of brain, breathing and heartbeat are synchronized. Moreover, respiration is bound to neural oscillations and memory formation. There is evidence, that timing conditioning stimuli to certain phases of breathing and heartbeat can modulate learning in trace eyeblink conditioning. Here we studied whether the timing of stimuli to different phases of respiration (expiration and inspiration) and heartbeat (systolic and diastolic) affects trace eyeblink conditioning in healthy adult humans. Based on our previous work, our hypothesis was that timing the conditioned stimulus (CS) to the systolic phase of the cardiac cycle during inspiration would deteriorate learning. In addition, we expected that timing the CS to the diastolic phase during expiration would be beneficial for learning. At last, we suspected that event-related potentials (ERPs) to the CS would differ between these two conditions.

We exposed adult male Sprague-Dawley rats to irradiation of the head, targeted especially to the hippocampus. Irradiation had only a minor effect on gut microbiota and no effect on systemic inflammation, synaptic plasticity in the hippocampus or hippocampal electrophysiology. However, as in previous studies, irradiation reduced adult hippocampal neurogenesis. Irradiation also impaired spatial recognition memory but no overall cognitive impairment was observed.

Rhythmic variation in heart rate and respiratory pattern are coupled in a way that optimizes the level of oxygen in the blood stream of the lungs and the body as well as saves energy in pulmonary gas exchange. It has been suggested that the cardiac cycle and respiratory pattern are coupled to neural oscillations of the brain. Yet, studies on how this rhythmic coupling is related to behavior are scarce. There is some evidence that, for example, the phase of respiration affects memory retrieval and the electrophysiological oscillatory state of the limbic system. It is also known that the phase of the cardiac cycle and hippocampal electrophysiological oscillations alone affect learning. Here, we studied whether the timing of training trials to different phases of respiration affects learning trace eyeblink conditioning in healthy adult humans. Trials consisting of a neutral conditioned stimulus (200‐ms tone) and a slightly aversive unconditioned stimulus (100‐ms air puff toward the eye), presented with a 600‐ms trace interval, were timed to either inspiration or expiration. A control group was trained regardless of respiratory phase. We found that, at the end of training, the rate of conditioned responses was higher in the group trained at expiration than it was in the other two groups. That is, brain state seems to fluctuate as a function of respiratory rhythm, and this fluctuation is also behaviorally relevant, exerting its effect on, at the least, a simple form of associative learning. peerReviewed

Fyysisesti aktiivisilla ikääntyneillä ihmisillä on pienempi riski sairastua muistisairauksiin, kuten Alzheimerin tautiin, ja liikuntaa on ehdotettu jopa muistisairauksien hoidoksi. Positiivinen yhteys aerobisen kunnon ja aivojen rakenteellisen kunnon välillä näkyy vielä yli 80-vuotiailla. Liikunnan vaikutuksia aivojen terveyteen ja oppimisen edellytyksiin tutkitaan nyt monitieteellisesti ja -menetelmällisesti. nonPeerReviewed

Hippocampal theta oscillations (3–12 Hz) play a prominent role in learning. It has been suggested that encoding and retrieval of memories are supported by different phases of the theta cycle. Our previous study on trace eyeblink conditioning in rabbits suggests that the timing of the conditioned stimulus (CS) in relation to theta phase affects encoding but not retrieval of the memory trace. Here, we directly tested the effects of hippocampal theta phase on memory retrieval in two experiments conducted on adult female New Zealand White rabbits. In Experiment 1, animals were trained in trace eyeblink conditioning followed by extinction, and memory retrieval was tested by presenting the CS at troughs and peaks of the theta cycle during different stages of learning. In Experiment 2, animals were trained in delay conditioning either contingent on a high level of theta or at a random neural state. Conditioning was then followed by extinction conducted either at a random state, contingent on theta trough or contingent on theta peak. Our current results indicate that the phase of theta at CS onset has no effect on the performance of the behavioral learned response at any stage of classical eyeblink conditioning or extinction. In addition, theta-contingent trial presentation does not improve learning during delay eyeblink conditioning. The results are consistent with our earlier findings and suggest that the theta phase alone is not sufficient to affect learning at the behavioral level. It seems that the retrieval of recently acquired memories and consequently performing a learned response is moderated by neural mechanisms other than hippocampal theta. peerReviewed

Aerobic exercise, such as running, has positive effects on brain structure and function, such as adult hippocampal neurogenesis (AHN) and learning. Whether high-intensity interval training (HIT), referring to alternating short bouts of very intense anaerobic exercise with recovery periods, or anaerobic resistance training (RT) has similar effects on AHN is unclear. In addition, individual genetic variation in the overall response to physical exercise is likely to play a part in the effects of exercise on AHN but is less well studied. Recently, we developed polygenic rat models that gain differentially for running capacity in response to aerobic treadmill training. Here, we subjected these low-response trainer (LRT) and high-response trainer (HRT) adult male rats to various forms of physical exercise for 6–8 weeks and examined the effects on AHN. Compared with sedentary animals, the highest number of doublecortin-positive hippocampal cells was observed in HRT rats that ran voluntarily on a running wheel, whereas HIT on the treadmill had a smaller, statistically non-significant effect on AHN. Adult hippocampal neurogenesis was elevated in both LRT and HRT rats that underwent endurance training on a treadmill compared with those that performed RT by climbing a vertical ladder with weights, despite their significant gain in strength. Furthermore, RT had no effect on proliferation (Ki67), maturation (doublecortin) or survival (bromodeoxyuridine) of new adult-born hippocampal neurons in adult male Sprague–Dawley rats. Our results suggest that physical exercise promotes AHN most effectively if the exercise is aerobic and sustained, especially when accompanied by a heightened genetic predisposition for response to physical exercise. peerReviewed

Hippocampal local field potentials are characterized by two mutually exclusive states: one characterized by regular θ oscillations (∼4–8 Hz) and the other by irregular sharp-wave ripples. Presenting stimuli during dominant θ oscillations leads to expedited learning, suggesting that θ indexes a state in which encoding is most effective. However, ripple-contingent training also expedites learning, suggesting that any discrete brain state, much like the external context, can affect learning. We trained adult rabbits in trace eyeblink conditioning, a hippocampus-dependent nonspatial task, followed by extinction. Trials were delivered either in the presence or absence of θ or regardless of hippocampal state. Conditioning in the absence of θ led to more animals learning, although learning was slower compared with a yoked control group. Contrary to expectations, conditioning in the presence of θ did not affect learning. However, extinction was expedited both when it was conducted contingent on θ and when it was conducted in a state contrary to that used to trigger trials during conditioning. Strong phase-locking of hippocampal θ-band responses to the conditioned stimulus early on during conditioning predicted good learning. No such connection was observed during extinction. Our results suggest that any consistent hippocampal oscillatory state can potentially be used to regulate learning. However, the effects depend on the specific state and task at hand. Finally, much like the external environment, the ongoing neural state appears to act as a context for learning and memory retrieval. peerReviewed

The relative power of the hippocampal theta-band (∼6 Hz) activity (theta ratio) is thought to reflect a distinct neural state and has been shown to affect learning rate in classical eyeblink conditioning in rabbits. We sought to determine if the theta ratio is mostly related to the detection of the contingency between the stimuli used in conditioning or also to the learning of more complex inhibitory associations when a highly demanding delay discrimination-reversal eyeblink conditioning paradigm is used. A high hippocampal theta ratio was not only associated with a fast increase in conditioned responding in general but also correlated with slow emergence of discriminative responding due to sustained responding to the conditioned stimulus not paired with an unconditioned stimulus. The results indicate that the neural state reflected by the hippocampal theta ratio is specifically linked to forming associations between stimuli rather than to the learning of inhibitory associations needed for successful discrimination. This is in line with the view that the hippocampus is responsible for contingency detection in the early phase of learning in eyeblink conditioning. peerReviewed