Understanding the nervous system is an important but perhaps ambitious goal, particularly for students in lower secondary education. It is important because of its’ direct role in both mental and physical health, and it is ambitious because instruction focuses on the human nervous system, which is extremely complex, and subject to numerous misconceptions. Despite its’ complexity, the science curricula, both nationally and internationally, emphasize an understanding of the system, and not just knowledge of isolated facts. But what does it mean to understand this system, and what content knowledge is critical for understanding it? Unfortunately, the curricula are usually too general to answer these questions, therefore other sources of information are needed. Using the science literature, the present study defines the system level of the nervous system and proposes three basic aspects necessary to understand it: 1) neural circuit architecture, 2) synaptic action, and 3) nerve signal origin. With this background, the aim of the present study is to identify lower secondary school students’ conceptions of these three aspects, and to determine how they impact students’ understanding of the system. To reach this aim, the study used a questionary which allowed for a mixed method design, and the results show that many students have an immediate conception of the brain as the origin of nerve signals. In addition, many students hold the alternative conceptions that 1) synaptic action is exclusively excitatory, and that 2) neural circuits consists of neurons connected in a chain, one single neuron after another. These alternative conceptions prevent students from understanding the system. Implications for instruction are discussed in the context of conceptual learning theories, and teaching strategies are proposed. Since similar curricula goals and textbook content exist in several countries, the present results may be representative across nations.